Charles River Research Models and Services 2013 / EUROPE

Transcription

1 Charles River Research Models and Services 2013 / EUROPE

2 Research Models and Services: The Charles River Tradition In 1947, a young veterinarian purchased thousands of rat cages from a Virginia farm and set up a one-man laboratory in Boston, overlooking the Charles River. He bred, fed and cared for the animals and personally delivered them to local researchers in need of laboratory animal models. Sixty-six years and 7,000 employees later, Charles River looks like a very different operation, but in Dr. Henry Foster s tradition of compassion, service and commitment to science, we remain unchanged. No matter how many employees and facilities we have assembled, we would have no reliable research without our animals. Our corporate history is rooted in the veterinary principles of Dr. Foster, and from that stems a deep commitment to the welfare of the research animals we breed and handle. Our scientists and technicians have cultivated a culture of humane treatment within our facilities around the globe through welfare training, animal safety awards and a programme to fund outside organisations whose missions focus on the welfare of laboratory animals. When possible, we look to refi ne traditional research methods in an effort to reduce the number of animals required for effective study. By investing in our Humane Care Initiative, as well as core programmes in Biosecurity, International Standardisation and Model Quality, we ensure research animals of superior health and genetic form, strengthening the long-term integrity of your research results. As we ve seen over our 66-year history, technologies evolve and diseases come and go. At Charles River, we believe it will be the same tenets on which we were founded that will carry us into the future: benevolence, resourcefulness and an urgency to advance human health by doing our part, no matter how big or small.

3 Charles River at a Glance Charles River continues its dedicated leadership in the life science community by providing academic, pharmaceutical, biotechnology, government and contract research organisations around the world with an ever-expanding portfolio that supports all therapeutic areas of research from drug discovery through market approval. Our complete line of products and services includes: Research Models p.11 Genetically Engineered Models and Services p.69 Preconditioning Services, Surgery and Contract Services p.45 Insourcing Solutions SM p.71 Research Animal Diagnostic Services p.55 For information on our additional offerings, including Preclinical Services, Discovery Research Services, Biopharmaceutical Services, Endotoxin & Microbial Detection and Agrochemical and Animal Health Product Development, visit

4 Table of Contents ORDERING INFORMATION RESEARCH MODELS OVERVIEW 6 Contacts and Ordering Information 7 Packaging 8 Health Monitoring System VAF/Plus health profile VAF/Elite health profile 9 Age/Weight correlation information Time mated and pregnant rodents Weight loss during transportation Humane Care Initiative 10 Quality Management Cancellation Policy OUTBRED RATS 11 CD IGS Lister Hooded 12 Long Evans OFA 13 Wistar Han IGS Wistar WI 14 Wistar WU Additional Models: CD Hairless INBRED RATS 15 Brown Norway Fischer 344 Lewis 16 WAG DISEASE AND TRANSLATIONAL MODELS METABOLIC, RENAL AND CARDIOVASCULAR MODELS 16 SHR Rats Wistar Kyoto WKY Rats 17 ZDF Rats Zucker Rats Bcrp Knockout Rats 18 PCK Rats ZSF1 Rats SHHF Rats GK Rats Cryopreserved Model ONCOLOGY MODELS 18 p53 Knockout Rats 19 Wistar Furth Rats Noble Rats Buffalo Rats BDIX Rats CENTRAL NERVOUS SYSTEM 19 Serotonin Transporter (SERT) Rat Nociceptin Receptor (OPRL 1) Rat Stroke Prone Rats OUTBRED MICE 21 CD-1 IGS MF1 22 NMRI OF1 23 SKH1 Additional Models : SKH3; Black Swiss THE JACKSON LABORATORY 24 JAX Mice and research services provided through Charles River INBRED MICE S2/SvPasCrl BALB/cJ (JAX Mice Strain) 27 BALB/cByJ(JAX Mice Strain) BALB/cAnNCrl 28 C3H/HeOuJ (JAX Mice Strain) C3H/HeNCrl 29 C57BL/6J (JAX Mice Strain) C57BL/6NCrl 30 CBA/CaCrl CBA/J (JAX Mice Strain) 31 DBA/1J (JAX Mice Strain) DBA/2J (JAX Mice Strain) DBA/2NCrl 32 FVB/NCrl SJL/J (JAX Mice Strain) B6 Albino HYBRID MICE 33 B6CBAF1/J (JAX Mice Strain) B6C3F1/Crl B6D2F1/NCrl 34 B6D2F1/J (JAX Mice Strain) CB6F1/Crl CD2F1/Crl NMRCF1/Crl DISEASE AND TRANSLATIONAL MICE METABOLIC, RENAL AND CARDIOVASCULAR MODELS 35 THE POUND MOUSE B6.V-Lep ob /J (ob/ob mice) (JAX Mice Strain) BKS.Cg-Dock7 m +/+Lepr db /J (db/db mice) (JAX Mice Strain) 36 B6.129P2-Apoe tm1unc /J (ApoE mice) (JAX Mice Strain) NOD Mice Cryopreserved Models INFLAMMATION AND IMMUNOLOGY MODELS 37 Ly5.1 Mouse OT I Mouse OT II Mouse Foxp3-IRES-mRFP (FIR) Mouse IL-4-IRES-eGFP (4get) Mouse 38 DBA/1J (JAX Mice Strain) Cryopreserved Model ONCOLOGY MODELS 38 P110 Ludwig Mouse NOD scid gamma (NSG) Mice (JAX Mice Strain) CENTRAL NERVOUS SYSTEM 38 PGP Mouse Cryopreserved Model JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. 4

5 Table of Contents IMMUNODEFICIENT MODELS 39 Nude mice BALB/c-Nude Mice 40 SCID Mice SHO Mice SCID Beige Mice 41 NOD SCID Mice (JAX Mice Strain) NOD scid gamma (NSG) Mice (JAX Mice Strain) 42 Nude Rats Other Immunodeficient Models Available RABBITS 43 New Zealand White GUINEA PIGS 43 Dunkin Hartley Hairless Guinea Pig HAMSTERS 44 Syrian Hamsters GERBILS 44 Gerbils PRECONDITIONING SERVICES, SURGERY AND CONTRACT SERVICES 45 Feeding studies Surgical and chemical manipulations Aging studies 46 Vascular catheters Non-Vascular catheters Excision surgery Disease models 47 Neurological procedures Device implantations Training Customised Surgical Procedures On-site Surgery From Surgery to Protocol 48 Biospecimens Tissues and Organs Blood Products 49 Antibody production protocols 50 ALZET Osmotic Pumps 52 Pharmaceutical quality control testing 53 Other quality control testing RESEARCH ANIMAL DIAGNOSTIC SERVICES 55 Mouse Health Monitoring Protocols Mouse Serology Profiles Mouse Microbiology 56 PRIA Panels for Mouse Health Surveillance/Quarantine 57 Rat Health Monitoring Protocols Rat Serology Profiles Rat Microbiology 58 PRIA Panels for Rat Health Surveillance/Quarantine 59 Rabbit/Gerbil Health Monitoring Protocols Rabbit Serology Profiles Gerbil Serology Profiles Rabbit/Gerbil Microbiology Cultures 60 Hamster/Guinea Pig Health Monitoring Protocols Hamster Serology Profiles Guinea Pig Serology Profiles Hamster/Guinea Pig Microbiology Cultures Miscellaneous Rodent Species Serology Profile 61 Individual Rodent/Rabbit Health Surveillance PCR Assays Rodent Parasitology Pathology Individual Agent Rodent/Rabbit Serology 62 Simian Testing Services Ferret Testing Services 63 Serology Reagents MFIA Reagents ELISA Reagents 64 IFA Reagents Serology Kits 65 Cell lines and Research Biologics Screening PCR Panels to Screen Cell lines and Research Biologics for Rodent Infectious Agents NEW Cell Line Examination and Report (CLEAR) Panel to detect cell line contamination 66 PCR Panels to Screen Cell lines and Research Biologics for Human Infectious Agents NEW Cell Line Examination and Report (CLEAR) Panel to detect cell line contamination In Vivo Biosafety Testing 67 Clinical Pathology Services Clinical Chemistry Profiles Environmental Monitoring GENETICALLY ENGINEERED MODELS AND SERVICES 69 Quarantine Breeding Rederivation 70 Cryopreservation Model creation services Genetic testing services INSOURCING SOLUTIONS 71 Staffing and Facility Management Expert Consulting Customized Training 72 Modular Buildings GLOSSARY OF TERMS 73 Glossary of Terms STRAIN INDEX 74 Strain index 81 Alphabetical Index JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. GENERAL TERMS AND CONDITIONS OF SALE 78 General terms and conditions of Sale Prices effective 1 st January

6 Ordering Information ORDERING INFORMATION Animals, products and services can be ordered from our customer service department by telephone, fax or . All orders must be confirmed by fax or . To ensure smooth processing of your order, we encourage you to use our order form available on request. Contact Details - Germany Charles River Research Models and Services, Germany GmbH Sandhofer Weg 7 - D Sulzfeld Tel: +49 (0) 9761/406-0 Fax: +49 (0) 9761/ [email protected] Contact Details - France Charles River - Customer Service Department Research Models and Services, France BP L Arbresle cedex (France) Tel: +33 (0) Fax: +33 (0) [email protected] Contact Details - Sweden NOVA-SCB AB Sweden Vibyvägen 72 Box 6023 S Sollentuna Tel: Fax: [email protected] Ordering Information Contact Details - Italy Charles River Research Models and Services, Italy Ufficio Ordini - Via Indipendenza Calco (Lecco) Tel: Fax: [email protected] Contact Details - Norway / Finland NOVA-SCB AS Norway Rauerskauveien 518 N-1482 Nittedal Tel: Fax: [email protected] Contact Details - United Kingdom Charles River Research Models and Services, U.K. Manston Road, Margate, Kent CT9 4LT Tel: +44 (0) Fax: +44 (0) [email protected] Contact Details - Spain Charles River Research Models and Services, Spain Av. Vía Augusta Building B2, 4 th floor, office 10 Sant Cugat Business Park Sant Cugat del Vallès - Barcelona Tel: Fax: [email protected] Geographical Area Phone number Fax number Switzerland (German speaking) +49 (0) 9761/ (0) 9761/ [email protected] Switzerland (French speaking) +33 (0) [email protected] Scandinavia Austria +49 (0) 9761/ (0) 9761/ [email protected] Eastern Europe Greece South Mediterranean [email protected] The Netherlands +33 (0) (0) [email protected] Belgium (English or French speaking) +33 (0) (0) [email protected] Ireland - Australia - India Middle East (Israel, Dubai, (0) [email protected] Kuwait, Saudi Arabia) New Zealand - Singapore Africa [email protected] Scandinavia Denmark +49 (0) (0) [email protected] Sweden (Malmo + Lund) +49 (0) (0) [email protected] Sweden [email protected] Norway [email protected] Finland [email protected] Spain [email protected] Portugal (English and Spanish speaking) +33 (0) [email protected] 6

7 Ordering Information PACKAGING French Shipping Crates Price - RATS / MICE / GUINEA-PIGS / HAMSTERS Novopack SPF - Rodents 21,90 Aeroplane Novopack wired cover 28,10 Safebox single SPF & SOPF Mice 14,00 Safebox large SOPF - Mice, Rats & GMO 28,50 Ico Metal III Axenic animals - germ free 50,00 RABBITS Duopack 24,30 PRECONDITIONED ANIMALS / SURGERY Novopack 21,90 Safebox single 14,00 Safebox large 28,50 BIOSPECIMENS On dry ice in isothermal container 80,00 Icepack container (+2 C+8 C) 24,30 Polystyrene container (isotherm) 20,50 DISPOSABLE DRY SHIPPER 114,50 ISOLATOR DELIVERIES Consult us EMPTY CRATES Consult us Novopack 38,95 Safebox Single 25,00 Safebox Large 47,05 Duopack 41,00 German Shipping Crates Price - RATS / MICE / GUINEA-PIGS / HAMSTERS Filter crate 20,50 Hydrogel 5,00 Safebox Single 20,50 Safebox Double 27,00 Safebox Large 33,50 RABBITS Filter crate 20,50 UK Shipping Crates Road - Air - Filtered 16,94 19,78 MiniShipper 11,08 13,76 Safebox Double 40,55 43,78 Williton Isolator 80,35 85,77 OverPack crate 17,14 18,86 Italy Shipping Crates Price - Filter box (SPF rodents) 20,10 Safebox single (SPF and SOPF Mice) 21,85 Safebox double (SPF and SOPF Mice) 34,00 Ready to use transport kits for health monitoring Price - Rats - Mice - Guinea pigs (1 reinforced shipper with filters and food) Safebox Single 28,80 Novopack 35,50 Safebox Large 54,10 OverPack Rabbits (1 reinforced shipper with filters and food) 44,75 PRIA Kit Serology Kit Enquire Enquire Animal Transport A carefully designed delivery plan taking into account times deliveries can be processed as quickly as possible. As a rule, deliveries are made in fully climate-controlled vans and trucks. The climate control systems in the trucks operate independently of the vehicle motor. Some export deliveries are transported by air freight. Transportation costs for animal orders are calculated according to the distance from our sites. Our customer service department can provide you with information regarding the transportation routes and corresponding costs. Transport of Blood, Serum and Plasma Transportation by our own delivery trucks or express service. 7

8 Research Models Overview RESEARCH MODELS OVERVIEW At Charles River, we understand that the quality of our research models has a direct impact on what truly matters to you your research. With our core programmes biosecurity, international standardisation, animal welfare and model quality you can focus on your work while being assured that you are receiving the highest quality and most reliable models for your research. From standard and disease-specific models to surgically altered animals, you can trust us to be an integral part of your research programmes now and in the future. Health Monitoring System Specific Pathogen Free (SPF) VAF Plus research models A basic requirement for the use of laboratory animals in biomedical research is the specification of their health status. For quality control, Charles River therefore carries out a routine health monitoring programmes with an examination protocol and methodology based on the FELASA recommendations (Federation of European Laboratory Animal Science Associations). The health monitoring system includes serologic testing and health checks. These include bacteriological, necropsy and parasitological analyses. Serological testing takes place every four weeks for all rodents. For rabbits, all monitoring including serology is performed quarterly. To check the integrity of the genetic profile for inbred and hybrid lines, biopsy samples are routinely studied using SNP analysis. This genetic monitoring programme is carried out every six months for inbred lines and quarterly for hybrids. The results of genetic monitoring are available on request. On our website ( the agents tested are separated into several categories: those monitored by serology, those monitored by bacteriology (culture and/or PCR) and those monitored by parasitology. Within these categories, attention should be paid to the letters in brackets following the name of the agent; these letters indicate which actions Charles River would take if the agent were detected and also the frequency of monitoring for that agent. The table below lists the rat and mouse agents which are specifically monitored by serology, microbiology or PCR for SPF/VAF Plus animals. RATS Sendai - SDA/RCV - KRV - H-1 - RMV - RPV1 - PVM - Reo-3 LCMV - MAV - Hantaan - CARB M. pulmonis - TMEV - H. hepaticus - H. bilis - Helicobacter spp. B. bronchiseptica - C. kutscheri - Salmonella spp. S. moniliformis - C. piliforme - Pasteurella multocida Pasteurella pneumotropica - Pneumocystis carinii - Encephalitozoon cuniculi - S. pneumoniae - ß haemolytic streptococci (A and G) MICE Sendai - PVM - MVM - MPV - TMEV - MHV - Polyoma MCMV - Reo-3 - Ectromelia - LCMV-MAV - K-EDIM - Hantaan - MTLV - CARB M. pulmonis - LDV - MNV - H. hepaticus - H. bilis Helicobacter spp. - C. rodentium - B. bronchiseptica - C. kutscheri - Salmonella spp. - S. moniliformis - C. piliforme Pasteurella multocida - Pasteurella pneumotropica Encephalitozoon cuniculi - ß haemolytic streptococci (A and G) - S. pneumoniae Specific and Opportunistic Pathogen Free (SOPF) - VAF Elite research models For immunodeficient models and sensitive models (like genetically-modified models or gamma-irradiated models) additional bioexclusion techniques are used to exclude the most important opportunistic agents. Most of those agents are carried by humans or present in the environment. They are nonpathogenic for immuno-competent rodents. For some immunodeficient or sensitive models, these agents might cause local or systemic infections. The additional agents tested for SOPF animals are : Staphylococcus aureus Proteus mirabilis Pseudomonas aeruginosa Klebsiella pneumoniae / oxytoca Non pathogenic protozoa Pneumocystis carinii Corynebacterium bovis Certain outbred and inbred mice with an SOPF health status can be ordered from Charles River. Specific strains are available across our European subsidiaries, see the strain index on page 74. Contact your local office for information on availabilities, pricing and reservations (see page 6). Axenic Rodents Axenic (or germ-free) rodents are hysterectomy-derived animals free of any detectable micro-organisms. Animals are prepared upon reservation only. What are the similarities between SPF and VAF Plus and between SOPF and VAF Elite Health Status? The SOPF and VAF Elite Health Status, and the SPF and VAF Plus Health Status, are based on the same health monitoring programmes in terms of agents screened, number and age of animals screened, frequency of testing, and recycling policies. In both cases, the name of the status differs for historical and geographic reasons. SPF and SOPF being more commonly used in continental Europe while VAF Plus and VAF Elite are more recognisable in the UK and North America. Contact your local technical support for a complete description of our health monitoring programmes. 8

9 Research Models Overview Strain Characteristics The various strains bred by Charles River have unique and intrinsic zootechnical and behavioural characteristics that have to be taken into account when ordering the models. For all questions related to strain characteristics, please contact our customer scientific and technical support. Aged Animals Aged animals are available from stock or upon reservation from 3 months up to 15 months for specific strains. The animals can be ordered by age ranges of 1 month. Specific strains are available across our European subsidiaries. Contact your local office for information on availabilities, pricing and reservations (see page 6). Mated and Pregnant Females, Litters We offer time mated and pregnant females for nearly all the strains raised at Charles River. The protocols used for time mating and pregnancy detection differ according to species and strain. Furthermore, transportation of pregnant animals and litters are subject to specific regulations. Please contact your local office (see page 6). Humane Care Initiative Charles River is committed to the humane care of the research animals produced and used in all of its activities. Our Humane Care Initiative supports this core value and is directed by our Animal Welfare and Training group. All Charles River s employees are engaged to this humane care policy: continued education, signature of an ethical commitment, internal audits, and ethical information feedbacks. Preconditioning Services and Contract Services Charles River preconditioning services allows researchers to save valuable resources by purchasing models ready for research. Preconditioning protocols range from standardised to individual protocols to suit customers requirements. Our preconditioning services offering is shown page 45. Surgical Services We offer a variety of surgical services, including vascular and nonvascular catheterisations, device implants and soft tissue, neurological and cardiovascular procedures, on three species rat, mouse, and guinea pig. Our comprehensive surgical services is shown page 46. Age/Weight Correlation Information Age/weight correlation information is presented throughout this product catalog for each sex of most stocks and strains. The information is specific to the conditions maintained in Charles River barrier production rooms. Weight information related to the JAX Mice strains are specific to the conditions maintained in Charles River s barrier production rooms as well. The shaded areas on each chart are the mean weight plus or minus one standard deviation at a given age averaged across all production facilities. This represents approximately 67% of the population, with the remaining 33% falling outside of this weight range. Overlaps in the full range of weights occur between age groups and will be more pronounced in outbred animals. Weight loss during transportation Please be aware that animals may lose up to 10% of their body weight during transportation. Animals will return to their approximate weight at shipment within 24 to 48 hours after arrival. This information is presented as guidance only as the rate of weight recovery may be strain-dependent and can also be influenced by the social position of the individual animals in their new hierarchies. Biospecimens Charles River can provide rat, mouse, guinea pig, hamster, gerbil and large species biospecimens upon request. Each order is priced individually based on the strain of animal desired and the complexity of the procedure. Our biospecimen offering is described page 48. Antibody production Charles River is a flexible and reactive partner for conduting your immunisation protocols, from research quantity to industrial production on a wide range of species from SPF rodents to large animals. The immunisation and sampling schedule can be adapted to customers specifications on request. Check our Antibody production services page 49. JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. 9

10 Research Models Overview Quality Management ISO 9001 V 2008 Charles River, Research Models and Services Germany (Kisslegg, Sulzfled), France (Oncins, Chatillon), Italy (Calco) and UK (Margate) are certified ISO These certifications apply to all products and services for all the facilities. Additional Charges - Specific orders Our research models are sold within specific weight ranges or at a certain age. For specific orders outside the standard weight range or age, additional charges may apply. Contact your local office (see page 6). Cancellation Policy Guinea-pigs: Cancellation accepted before the guinea-pigs are weaned (2 weeks). ISO 9001:2008 Rabbits: Time mated females 4 weeks before mating date, we invoice the price of an animal of 14 weeks old. GMP, cgmp, ISO Charles River France is also ISO accredited, GMP compliant, registered to the FDA and work in cgmp compliant environment for others specifics activities. For further information, contact your local office (see page 6). Ethic Management: AAALAC Charles River facility in Margate, UK, received in July 2010 full accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. Charles River Margate is the first and only commercial small animal breeder in the UK to receive AAALAC accreditation. 2 weeks before mating date, we invoice the price of an animal of 16 weeks old. 1 week before mating date, we invoice the price of an animal of 18 weeks old. 1 day before mating date, we invoice the price of a time mated female. Other rabbits: Cancellation accepted before they are 10 weeks old. Rodents: Standard outbred/inbred strain and standard age/weight range (catalogue strain < 8 weeks old): no cancellation fee before animals are prepared for dispatch. Standing orders: 6 weeks notice for cancellation/modification Specific strains and special age/weight range: no cancellation allowed, Take or pay Mated/pregnant females (standard strains OFA, CD, WISTAR, OF1, and CD1): no cancellation fee if the order is cancelled before mating. After mating, invoice at the price list cost. Other strains / specific orders (large quantities, age range ): invoice of cost up to the date of cancellation. 10

11 Rat Models Rat Models Charles River is dedicated to providing you with consistent availability of the highest quality research models globally. Our comprehensive portfolio of outbred, inbred and disease/translational rat models enables you to select the appropriate animal model for your research.

12 Rat Models Outbred Rat Models Common Name Nomenclature Page CD IGS Crl:CD(SD) 11 Lister Hooded Crl:LIS 11 Long Evans Crl:LE 12 OFA Crl:OFA(SD) 12 Wistar Han IGS Crl:WI(Han) 13 Wistar Crl:WI 13 Wistar WU Crl:WI(WU) 14 CD Hairless Crl:CD-Prss8 hr 14 Inbred Common Name Nomenclature Page Brown Norway BN/Crl 15 Fisher 344 F344/lcoCrl 15 Fisher 344 F344/DuCrl 15 Lewis LEW/Crl 15 WAG WAG/RijCrl 16 Disease and Translational Models Metabolic, Renal and Cardiovascular Models Common Name Nomenclature Page SHR SHR/NCrl 16 Wistar Kyoto WKY/NCrl 16 ZDF ZDF-Lepr fa /Crl 17 Zucker Crl:ZUC(Orl)-Lepr fa & Crl:ZUC-Lepr fa 17 Bcrp Knockout Crl:WI(UL)-Abcg2 m1/hubr 17 PCK PCK/CrljCrl-Prkhd1 pck /Crl 18 ZSF1 ZSF1-Lepr fa Lepr cp /Crl 18 SHHF SHHF/MccGmiCrl-Lepr cp /Crl 18 GK GK/TohiCskCrljCrl 18 Cryopreserved Model - Rip-HAT CD:SD-Tg(ins2-IAPP)Soel 18 Oncology Models Common Name Nomenclature Page p53 Knockout Crl:WI(UL)-Tp53 tm1/hubr 18 Wistar Furth WF/lcoCrl 19 Noble NBL/CrCrl 19 Buffalo BUF/CrCrl 19 BDIX BDIX/OrlCrl 19 Central Nervous System Common Name Nomenclature Page Serotonin Transporter (SERT) WI(HAN)-Slc6a4 1Hubr /Crl 19 Nociceptin Receptor (OPRL 1) Crl:WI(Han).BN-OPRL1 1Hubr 19 Stroke Prone SHRSP/A3NCrl 19

13 Outbred Rats CD IGS (International Genetic Standard) Rat Crl:CD(SD) FE Weight in Grams Price - Price - <50 8,15 8, ,84 8, ,27 11, ,59 12, ,74 13, ,93 14, ,62 16, ,72 17, ,66 18, ,88 19, ,09 Enquire 301+ Enquire Enquire Retired breeder Enquire Enquire Pregnant / time mated females Enquire Female with litter (males or females) Enquire ORIGIN Originated in 1925 by Robert W. Dawley from a hybrid hooded male and a female Wistar rat. Introduced into Charles River in 1950 from Sprague Dawley. Caesarean derived in 1955 from original Charles River SD colonies to form the nucleus of the current CD stock. Production colonies are developed from the Foundation Colony and managed according to the Charles River International Genetic Standard breeding system. COAT COLOR White (Albino). Lister Hooded Crl:LIS FE Weight in Grams Price - Price - <50 12,64 12, ,10 14, ,70 15, ,28 17, ,01 19, ,73 20, ,58 22, ,56 24, ,55 26, ,52 28, ,64 30, Enquire Enquire Retired breeder 17,74 17,74 Pregnant / time mated females Female with litter (males and females) Enquire Enquire ORIGIN These rats have taken their name from the Lister Institute, where the stock first originated. From Glaxo to Charles River UK in 1990 and again in To Charles River Germany in Noted for its docility and good breeding performance. Susceptible to audiogenic seizures. COAT COLOR White with black hood. 11

14 Outbred Rats Long Evans Rat Crl:LE FE Age in Weeks Price - Price ,65 23, ,19 28, ,38 31, ,03 35,03 ORIGIN Originated by Drs. Long and Evans in 1915 by cross of several Wistar Institute white females with a wild gray male. To Charles River from Canadian Breeding Farm and Laboratories in Caesarean rederived in COAT COLOR White with black hood; occasionally white with brown hood. OFA Rat Crl:OFA(SD) FE Weight in Grams Price - Price - <50 7,69 7, ,30 8, ,00 10, ,13 11, ,10 12, ,19 13, ,09 14, ,36 15, ,64 Enquire ,43 Enquire , Enquire - Retired breeder - 12,30 Pregnant / time mated females - Enquire Female with litter (males or females) - Enquire Axenic animals - Enquire Ageing rats - Enquire ORIGIN The original strain was composed in 1925 by Robert Worthington Dawley. Carworth Farms obtained it in 1955 and renamed it CFE (Carworth Farms Elias).Transferred to Charles River France in 1967, it then became known as OFA (Oncins France Strain A), in COAT COLOR White (Albino). 12

15 Outbred Rats Wistar Han IGS (International Genetic Standard) Rat Crl:WI(Han) FE Weight in Grams Price - Price - < 50 7,93 7, ,10 9, ,39 11, ,68 12, ,97 13, ,40 15, ,76 16, ,84 Enquire ,87 Enquire , , Enquire Retired breeder Enquire Enquire Pregnant / time mated females Enquire Female with litter (males or females) Enquire ORIGIN Rederived by Glaxo Wellcome from Han Wistar stock supplied by BRL. Transferred to Charles River in Production colonies are developed from the Foundation Colony and managed according to the Charles River International Genetic Standard breeding system. COAT COLOR White (Albino). Wistar Rats Crl:WI FE Weight in Grams Price - Price - < 50 8,08 8, ,27 9, ,62 11, ,93 12, ,24 14, ,70 15, ,08 17, ,19 Enquire ,24 Enquire , , Enquire Retired breeder Enquire Enquire Pregnant / time mated females Enquire Female with litter (males and females) Enquire ORIGIN To Scientific Product Farms Ltd (previous owner of Charles River UK) in 1947 from Wistar Institute. To Charles River USA in 1975 from Charles River UK. Caesarian derived in 1975 to form the nucleus of the current Wistar rat colonies. COAT COLOR White (Albino). 13

16 Outbred Rats Wistar Wu Rat Crl:WI(WU) FE Weight in Grams Price - Price ,78 10, ,52 12, ,88 13, ,47 15, ,67 16, ,85 17, ,34 Enquire ,43 Enquire ,06 Enquire Enquire Enquire Retired breeder Enquire 16,84 Pregnant / time mated females Enquire Female with litter (males and females) Enquire ORIGIN Selection by H.H. Donalson at the Wistar-Institute, USA, at the begining of 19th century. To Glaxo in 1927, continued as inbred. To Nederlands-Institute voor Volksfoending in 1933, to Unilever, Vlaardingen in 1941 and Institut Centraale Proefdierenbedrijf TNO in Caesarean rederived in As an outbred to SAVO, Kißlegg in Caesarean rederived at Charles River in COAT COLOR White (Albino). Additional Models CD Hairless NOMENCLATURE Crl:CD-Prss8 hr Limited availability, upon reservation from Charles River USA 14

17 Inbred Rats INBRED RATS Brown Norway Rats BN/Crl FE Age in Weeks Price - Price ,88 30, ,04 33, ,32 36, ,81 40, ,68 45, ,84 47,84 Additional week 6,00 6,00 ORIGIN Silvers and Billingham began brother x sister matings with selection for haplotype in 1958 from a brown mutation in a stock of wild rats maintained by King and Aptekman in a pen-bred colony rats trapped from the wild in 1930 by King at the Wistar Institute. To Charles River from Radiobiology Institute, Netherlands in COAT COLOR Non-agouti brown. Fischer 344 Rats F344/IcoCrl F344/DuCrl F344/IcoCrl F344/DuCrl & FE & FE Age in Weeks Price - Price ,73 16, ,98 20, ,26 21, ,20 25, ,90 28, ,83 32,06 Additional week 3,30 3, NOMENCLATURE F344/IcoCrl ORIGIN From mating #344 of rats purchased from a local breeder (Fischer). The colony was originated by M. R. Curtis, Columbia University in To the Germ-Free Animal Laboratory at CNRS, Gif-sur-Yvette, France from the Lobund Institute, University of Notre-Dame, South Bend, Indiana, U.S.A. Subsequently introduced to Charles River France in 1970 as an axenic colony. COAT COLOR Albino. BREEDING LOCATION France. NOMENCLATURE F344/DuCrl ORIGIN From mating #344 of rats purchased from a local breeder (Fischer). Colony originated by M.R. Curtis, Columbia University Institute for Cancer Research, Dunning at Columbia continued to inbreed to form the strain starting in Dunning to Charles River in 1960 at F68. Caesarean rederived in To Charles River Germany in COAT COLOR Albino. BREEDING LOCATION Germany, USA Lewis Rats LEW/Crl FE Age in Weeks Price - Price ,65 21, ,52 25, ,76 27, ,76 30, ,87 34,87 Additional week 3,30 3,30 ORIGIN Developed by Dr. Lewis from Wistar stock in the early 1950s. To Charles River from Tulane in 1970 at F34. Hysterectomy rederived in COAT COLOR Albino. 15

18 Inbred Rats / Disease and Translational Models WAG Rats WAG/RijCrl FE Age in Weeks Price - Price ,69 20, ,09 23, ,74 25, ,03 28, ,02 31,02 8 Enquire Enquire ORIGIN A.L. Bacharach, Glaxo Labs., U.K., 1924, from a Wistar stock. To Harrington in 1964 at F83. To MBL-TNO in 1953, after that to REP Institutes TNO, Rijswijk. To Charles River Germany from REP Institutes TNO in COAT COLOR Albino. METABOLIC, RENAL AND CARDIOVASCULAR MODELS SHR Rats SHR/NCrl FE Age In Weeks Price - Price ,92 60, ,79 64, ,70 70, ,03 79, ,84 86, ,12 96, ,86 103, ,75 110,75 Additional week 6,23 6,23 ORIGIN To NIH in 1966 from Okamoto at F 13. From an outbred Wistar Kyoto male with marked elevation of blood pressure. To Charles River from NIH in 1973 at F 32. Caesarean derived in COAT COLOR Albino. Wistar Kyoto Rats WKY/NCrl FE Age In Weeks Price - Price ,57 21, ,58 26, ,26 29, ,40 34, ,15 40, ,59 43,59 Additional week 6,34 6,34 ORIGIN Strain started by Okamoto from outbred Wistar stock at the Kyoto School of Medicine, in To NIH in This is the same stock from which the SHR was developed. To Charles River in 1974 at F11. COAT COLOR Albino AGE IN DAYS 16

19 Disease and Translational Models ZDF Rats ZDF-Lepr fa /Crl FE Age in Weeks Diabetic fa/fa - Control?/+ - Diabetic fa/fa - Control?/ ,67 138,11 253,96 138, ,55 150,81 266,54 150, ,86 162,08 277,55 162, ,13 173,94 291,39 173, ,20 186,69 302,08 186,69 Additional week 6,62 6,62 6,62 6,62 ORIGIN The diabetic trait occured in a colony of outbred Zucker rats at Eli Lilly Research Laboratories, USA, during Part of this colony was moved to Indiana University Medical School (IUMS) in Animals with diabetic lineage were identified and rederived in The inbred line of ZDF rat was established in To Genetic Models Inc. (GMI) in 1991 and to Charles River in COAT COLOR White with black hood. DIET PURINA PCR testing required to establish zygosity for orders below 6 weeks. ZDF Control Information Due to the ZDF rat breeding system, lean animals of two genotypes (fa/+ and +/+) are available as possible controls. When you order?/+ controls, the zygosity is not determined as the models are selected by observation of lean phenotype. Therefore fa/+ or +/+ controls might be delivered to you as lean controls. If you need a confirmed genotype for your controls, PCR testing costs are added to the price of the animals. Contact us for a specific quotation if confirmed fa/+ or +/+ genotypes are required. It is a condition of sale that customers (or their employees) purchasing or receiving ZDF rats are not permitted to breed or cross breed ZDF rats without the prior written approval of Charles River. Zucker Rats Crl:ZUC(Orl)-Lepr fa Crl:ZUC-Lepr fa /FE /FE Age In Weeks Fatty fa/fa - Control fa/ ,91 35, ,86 39, ,38 43,94 Additional week 3,23 3,39 NOMENCLATURE Crl:ZUC(Orl)-Lepr fa ORIGIN The spontaneous mutation obese (Fatty) was found in the 13 M rat stock of Sherman and Merck, by Doctor Lois Zucker, Harriet Bird Memorial Laboratory, Stow, Massachusetts 01775, USA, in The strain was introduced in Orléans at CSEAL, France in 1970; then transferred to Charles River France in COAT COLOR Agouti. NOMENCLATURE Crl:ZUC-Lepr fa ORIGIN The obese or fatty condition appeared in the 13M strain maintained at the Laboratory of Comparative Pathology of Theodore and Lewis Zucker in Stow, MA, USA. Research colonies were established at many institutions from this nucleus colony. To Charles River USA in 1985 from a research colony maintained at a pharmaceutical company. COAT COLOR Four principal coat color variants: 1 predominantly brown, 2 brown and white dilute, 3 predominantly black, 4 black and white. MEAN WEIGHT +/- 1 STANDARD DEVIATION FOR GUIDANCE ONLY FE Bcrp Knockout Rats Crl:WI(UL)-Abcg2 m1/hubr /FE /FE /FE Age in Weeks Homozygous Heterozygous Wildtype Up to Consult us Consult us Consult us 11+ ORIGIN At the Hubrecht Institute a nonsense mutation at amino acid position 59 (Glu to stop) within the catalytic center ABC transporter-like domain of the rat Abcg2 (Bcrp) gene was isolated which eliminates all wild-type protein. Transferred to Charles River under exclusive license from Transposagen in COAT COLOR White (Albino). RESEARCH APPLICATION ADME, Drug transport, Toxicology, Pharmacokinetics, Bioavailability, Blood-brain barrier transport, Stem cells, Progenitor cells, Proliferation, Differentiation, Tumor initiating cells, Phototoxicity, Protoporphyria, Hypoxia. 17

20 Disease and Translational Models Polycystic Kidney Disease Rats* PCK/CrljCrl-Prkhd1 pck /Crl FE Age in Weeks Price - Price - <4 59,82 59, ,25 64, ,58 67, ,01 72, ,22 74,22 Additional week On request On request ORIGIN In 2005, Charles River brought the PCK Rat, a polycystic kidney disease rat model, to the United States from our production facility in Japan. Polycystic kidney disease is a hereditary disorder that develops in both infants and adults. The infant form results from an autosomal recessive gene, whereas the adult onset of this disease is caused by an autosomal dominant gene. The PCK Rat is an inbred strain which carries the Pkhd1splicing mutation and is a model of the autosomal recessive polycystic kidney disease (ARPKD). Characterised by progressive cystogenesis and impairment of renal function, this model was first identified in a colony of CD rats at the Charles River production facility in Japan. * Only available as an import, Prices are subject to exchange rate variation. It is a condition of sale that customers (or their employees) purchasing or receiving PCK rats are not permitted to breed or cross breed PCK rats without the prior written approval of Charles River. Additional Models ZSF1 Rats* NOMENCLATURE ZSF1-Lepr fa Lepr cp /Crl It is a condition of sale that customers (or their employees) purchasing or receiving this strain are not permitted to breed or cross breed this strain without the prior written approval of Charles River. Spontaneously Hypertensive Heart Failure (SHHF) model Rats* NOMENCLATURE SHHF/MccGmiCrl-Lepr cp /Crl GK Rats* NOMENCLATURE GK/TohiCskCrljCrl Cryopreserved Model: RIP-HAT* NOMENCLATURE CD:SD-Tg(ins2-IAPP)Soel This model may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc. * Limited availability, upon reservation from Charles River US. ONCOLOGY MODELS p53 Knockout Rats Crl:WI(UL)-Tp53 m1/hubr / FE / FE Age in Weeks Heterozygous* Wildtype Up to Consult us Consult us * Homozygous animals available in limited quantities. Please inquire for pricing. ORIGIN At the Hubrecht Institute a nonsense mutation at amino acid position 273 (Cys to stop) within the DNA binding domain of the rat p53 gene was isolated, which resulted in a full knockout mutation. Transferred to Charles River under exclusive license from Transposagen in COAT COLOR White (Albino). RESEARCH APPLICATION Oncology, Toxicology, Carcinogenicity. 18

21 Disease and Translational Models Wistar Furth Rats WF/IcoCrl FE Age in Weeks Price - Price ,09 54, ,09 54, ,86 55, ,18 59, ,54 60, ,43 64,43 Additional week 6,50 6,50 ORIGIN Furth developed this strain at Roswell Park Memorial Institute, Buffalo, NY, USA in 1945 starting from a commercial colony of Wistar rats. Acquired by Charles River from the Microbiological Associates, Bethesda, Maryland, USA. Introduced to Charles River France in COAT COLOR Albino. Additional Models Noble Rats NOMENCLATURE NBL/CrCrl Cryopreserved strain, please contact us. Buffalo Rats NOMENCLATURE BUF/CrCrl Limited availability, upon reservation from Charles River USA. BDIX Rats NOMENCLATURE BDIX/OrlCrl On request. Please contact us. CENTRAL NERVOUS SYSTEM (CNS) MODELS Serotonin Transporter (SERT) Rats NOMENCLATURE WI(Han)-Slc6a4 1Hubr /Crl ORIGIN This strain was created in the laboratory of Dr. Edwin Cuppen at the Hubrecht laboratory in the Netherlands. Biochemical characterisation revealed that SERT mrna and functional protein are completely absent in homozygous knock-out rats and that there is a gene dose-dependent reduction in the expression and function of the SERT in heterozygous knock-out rats. For any requests and orders, please contact: [email protected] Nociceptin Receptor (OPRL 1) Rats NOMENCLATURE Crl:WI(Han).BN-OPRL1 1Hubr ORIGIN This strain was created in the laboratory of Dr. Edwin Cuppen at the Hubrecht Institute in the Netherlands. Biochemical characterization revealed that the OPRL1 functional protein (Nociceptin Receptor) is completely absent in homozygous knock-out rats and that there is a gene dose-dependent reduction in the expression and function of the Nociceptin Receptor in heterozygous knock-out rats. No adaptative change in other opioid receptor levels (kappa, delta, mu) could be demonstrated. For any requests and orders, please contact: [email protected] Additional Models Stroke Prone Rats NOMENCLATURE SHRSP/A3NCrl Limited availability, upon reservation from Charles River USA. 19

22 20

23 Mouse Models Mouse Models With more than 100 strains of mouse models, Charles River is positioned to provide you with the mouse models you require to meet your programme goals. Our global network of production facilities ensures that you have consistent access to these models, regardless of location.

24 Mouse models Mouse Models Outbred Common Name Nomenclature Page CD-1 IGS Crl:CD1(ICR) 21 MF1 Crl:MF1 21 NMRI Crl:NMRI(Han) 22 OF1 Crl:OF1 22 SKH1 Hairless Crl:SKH1-Hr hr 23 Black Swiss Crl:NIHBL(SW) 23 Inbred Common Name Nomenclature Page S2/SvPasCrl 26 BALB/cJ* BALB/cJ 26 BALB/cByJ* BALB/cByJ 27 BALB/cN BALB/cAnNCrl 27 C3H/HeOuJ* C3H/HeOuJ 28 C3H/N C3H/HeNCrl 28 BL/6J* C57BL/6J 29 BL/6N C57BL/6NCrl 29 CBA/Ca CBA/CaCrl 30 CBA/J* CBA/J 30 DBA/1J* DBA/1J 31 DBA/2J* DBA/2J 31 DBA/2NCrl DBA/2NCrl 31 FVB FVB/Ncrl 32 SJL* SJL/J 32 B6 Albino B6N-Tyr c /BrdCrCrl 32 Hybrid Common Name Nomenclature Page B6CBAF1/J* B6CBAF1/J 33 B6C3F1/Crl B6C3F1/Crl 33 B6D2F1/NCrl B6D2F1/NCrl 33 B6D2F1/J* B6D2F1/J 34 CB6F1/Crl CB6F1/Crl 34 CD2F1/Crl CD2F1/Crl 34 NMRCF1 NMRCF1/Crl 34 Disease and Translational Mice Metabolic, Renal and Cardiovascular Models Common Name Nomenclature Page THE POUND MOUSE C57BL/6NCrl- Lepr db-lb /Crl 35 ob/ob mice* B6.V-Lep ob /J 35 db/db mice* BKS.Cg-Dock7 m +/+ Lepr db /J 35 ApoE mice* B6.129P2- Apoe tm1 Unc/J 36 NOD* NOD/ShiLtJ 36 Cryopreserved Models 36 Inflammation and Immunology Models Common Name Nomenclature Page Ly5.1 B6.SJL-Ptprc a Pepc b / BoyCrl 37 OT I C57BL/6-Tg(TcraTcrb) 1100Mjb/Crl 37 OT II C57BL/6-Tg(TcraTcrb) 425Cbn/Crl 37 Foxp3-IRES-mRFP (FIR) C57BL/6J- Foxp3 tm1flv /Crl 37 IL-4-IRES-eGFP (4get) C.129X1-Il4 tm1lky & B6.129X1-Il4 tm1lky /Crl 37 DBA/1J* DBA/1J 38 Cryopreserved Model 38 Oncology Models Common Name Nomenclature Page P110 Ludwig 38 NOD scid gamma (NSG)* NOD.Cg-Prkdc scid Il2rg tm1wjl /SzJ Central Nervous System Common Name Nomenclature Page PGP Crl:CF1-Abcb1a mds 38 Cryopreserved Model 38 * JAX Mice strains. 38

25 Outbred Mice CD-1 IGS (International Genetic Standard) Mice Crl:CD1(ICR) FE Weight in Grams Price - Price ,35 3, ,47 3, ,76 3, ,04 4, ,25 4, ,60 4, ,81 4,81 > 24 g / (per 2 g) Enquire Enquire Retired breeder Enquire Enquire Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire ORIGIN The original group of Swiss mice that served as progenitors of this stock consisted of two male and seven female albino mice derived from a non-inbred stock in the laboratory of Dr. de Coulon, Centre Anticancereux Romand, Lausanne, Switzerland. These animals were imported into the United States by Dr. Clara Lynch of the Rockefeller Institute in The Hauschka Ha/ICR stock was initiated in 1948 at the Institute for Cancer Research in Philadelphia from Swiss mice of Rockefeller origin. To Dr. Edward Mirand of Roswell Park Memorial Institute where they were designated as HaM/ICR. To Charles River in 1959 and hysterectomy rederived that same year. Production colonies are developed from the Foundation Colony and managed according to the Charles River International Genetic Standard breeding system. COAT COLOR Albino MF1 Mice Crl:MF1 FE Weight in Grams Price - Price ,30 4, ,49 4, ,58 4, ,74 4, ,83 4, ,90 4, ,99 4, ,14 5, ,31 5,31 Add per 3 g 0,82 0,82 Untimed pregnant 32,73 Female with litter 46,44 Proven breeder 12,86 12,86 Ex-breeder 3,99 3,99 ORIGIN These albino mice, which were originally developed at Olac prior to 1970, came from a cross between the Laboratory Animal Centre A-strain mice ( LACA - but formerly called CFW) and the CS1 from Scientific Products Farm (acquired by Charles River). The stock was rederived by Charles River in 2004 and subsequently transferred to Charles River UK in April COAT COLOR Albino. 21

26 Outbred Mice NMRI Mice Crl:NMRI(Han) FE Weight in Grams Price - Price ,51 3, ,77 3, ,01 4, ,27 4, ,52 4, ,99 4, ,22 5,22 > 24 g / (per 2 g) Enquire Enquire Retired breeder Enquire Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire ORIGIN Swiss-type mouse, which Clara Lynch gave to Poiley in He maintained an inbred line of this animal until the 51 st generation, before he transferred it to the Naval Medical Research Institute. Introduced into Charles River in 1979 from the Central Institute for Laboratory Animal Breeding - Hannover (Germany). COAT COLOR Albino. OF1 Mice Crl:OF1 FE Weight in Grams Price - Price ,04 3, ,27 3, ,34 3, ,54 3, ,77 3, ,99 3, ,35 4,35 > 24 g / (per 2 g) Enquire Enquire Retired breeder 2,82 2,82 Time mated females 32,62 Female with litter (males and females) 54,58 Pregnant females 37,14 ORIGIN In 1935,Carworth Farms began to select a line of vigorous and productive mice. Progenitors originating from a colony bred in Missouri were bought and the strain was named CF1 (Carworth Farms strain 1). This strain was introduced at Charles River France in 1967, and it acquired the name OF1 (Oncins France 1). COAT COLOR Albino

27 Outbred Mice SKH1 Hairless Mice Crl:SKH1-Hr hr FE Age in Weeks Price - Price ,05 30, ,95 31, ,03 34, , ,45 Additional week 2,30 2,30 ORIGIN An uncharacterised / non-pedigreed hairless strain of mice was acquired by Temple University from a small commercial supplier in New York City. To Charles River from the Skin and Cancer Hospital, Temple University in The mouse is euthymic and immunocompetent. COAT COLOR Hairless, albino. SKH3 (Crl:SKH3(SKH2)-Hr hr ) MICE ALSO AVAILABLE ON REQUEST: CONSULT US. Additional Models Black Swiss NOMENCLATURE Crl:NIHBL(SW) Limited availability, upon reservation from Charles River USA. 23

28 The Jackson Laboratory JAX MICE AND RESEARCH SERVICES PROVIDED THROUGH CHARLES RIVER The Jackson Laboratory and Charles River, Inc. have a cooperative agreement to provide local supplies of JAX Mice to biomedical researchers in many European and Asian countries. Through this agreement, Charles River serves as the exclusive, authorised, commercial distributor and breeder of JAX Mice strains in the countries listed below. Austria Hungary Poland Belgium Ireland Portugal China Italy Spain Czech Republic Japan Sweden Denmark Korea Switzerland Finland Luxembourg Taiwan France Netherlands United Kingdom Germany Norway JAX Mice are The Gold Standard for Biomedical Research Used by researchers around the world, JAX Mice are the most frequently cited strains in biomedical research publications and are supported by world-renowned scientific and technical staff. JAX Mice are produced according to the highest standards of animal health and genetic quality. Charles River provides researchers in Europe and Asia with expedited access to over 6,000 JAX Mice strains and hundreds of new mouse models each year. JAX Mice strains include commonly used inbred strains as well as thousands of specialised disease models and genetically engineered strains. JAX Mice are The Most Published, Best Characterised Mouse Models JAX Mice have been referenced in more than 30,000 peer reviewed publications. Over 11,000 PubMed references cite use of the authentic JAX Mice B6 strain (C57BL/6J, stock number ). The JAX Mice B6 strain, along with many other JAX Mice inbred strains have been fully sequenced as part of the Mouse Genome Project (see: The genome sequence data of JAX Mice strains will remain relevant over time due to the rigorous genetic quality programs (including the JAX patented Genetic Stability Program) used to breed JAX Mice Strains. Additional genetic and phenotypic information about JAX Mice is publicly available in data resources hosted by The Jackson Laboratory, including Mouse Genome Informatics ( and The Mouse Phenome Database ( Assure genetic quality through routine use of state-of-the-art genetic quality monitoring methods such as SNP analysis. Under these conditions, JAX Mice strains bred by Charles River are: Equivalent in genetic quality to those bred by The Jackson Laboratory Provide the genetic integrity and stable phenotypes needed to support research excellence. J Substrains Differ from Authentic JAX Mice Strains due to Genetic Drift Over the years, organisations around the world have been maintaining colonies of mouse substrains with JAX Mice ancestry ( J substrains). These J substrains differ from JAX Mice strains due to the genetic mutations which spontaneously occur and accumulate in mouse breeding colonies over time. Due to naturally occurring genetic drift, a mouse strain will diverge into a genetically distinct substrain if its breeding colony is separated from the parental breeding colony for more than 20 generations of breeding (i.e., 10 generations in the parent colony plus the 10 that simultaneously pass in the sub-colony*). This divergence can occur within only a few years. Genetic differences between a parental strain and a substrain accumulate with time and at a rate dependent upon the level of quality control at the facilities housing and breeding the mice. These genetic differences often result in phenotype differences between a parental strain and a substrain. Such differences confound interpretation of experimental results especially when comparing results to published research based on using JAX Mice strains. IMPORTANT NOTE: JAX Mice strains bred by Charles River are authentic JAX Mice and are NOT genetically drifted J substrains. * For more information on mouse nomenclature and substrain divergence, see Only JAX Mice Strains bred by Charles River in Europe and Japan are equivalent in genetic quality to those bred by The Jackson Laboratory. Charles River in Europe and Japan breed JAX Mice in strict adherence to The Jackson Laboratory s breeding protocols and genetic quality control guidelines. These protocols provide the following benefits: Minimise naturally occurring genetic drift by systematically reinfusing breeding colonies with pedigreed mice from The Jackson Laboratory. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 24

29 The Jackson Laboratory Patented Genetic Stability Program The JAX patented Genetic Stability Program (GSP) effectively prevents cumulative genetic drift, including that caused by copy number variation, in the most popular strains of JAX Mice. The GSP program effectively limits cumulative genetic drift by refreshing The Jackson Laboratory s foundation stocks with cryopreserved pedigree embryos or gametes approximately every five generations (Figure 1). The program was initiated in 2003 (Taft et al. 2006) and is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. The Jackson Laboratory Frozen embryos used to refresh foundation stock every five generations Cryopreserved Stocks Foundation Stock Charles River European breeding sites Expansion & Distribution Jackson Laboratory production colonies Figure 1: Foundation stocks of several broadly-used JAX Mice strains are refreshed with cryo-recovered stocks every five generations. The Jackson Laboratory s unique, patented GSP has several components: 1) an extensive supply of cryopreserved stock for each strain; 2) isolated foundation colonies, maintained by inbreeding for only five generations before refreshing with cryo-recovered stock; 3) large, independent expansion and production colonies fed directly from pedigreed colonies for distribution through The Jackson Laboratory and through Charles River in Europe and Japan. Importantly, the generations between the cryopreserved stocks and mice produced for distribution are kept to a minimum to prevent the accumulation of mutations that result in genetic drift (see: * The Jackson Laboratory s innovative Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. Importance of Indicating Strain Lineage and History using Proper Strain Nomenclature Proper mouse strain nomenclature, as established by the International Committee on Standardised Genetic Nomenclature for Mice, provides researchers with essential information about the lineage and history of inter-laboratory transfers of substrains over time. Using proper strain nomenclature requires including in the strain name all Laboratory Codes (i.e., a unique 2-4 letter code assigned to each investigator or institution) as a means to identify all investigators or institutions which have maintained a strain or substrain. For a complete list of Laboratory Codes, see: Research Services Using JAX Mice Charles River breeding facilities located in Europe and Japan also serve as The Jackson Laboratory s exclusive commercial providers of research services using JAX Mice bred by Charles River. Services offered include: Biospecimen provision Cross-breeding Custom breeding Dedicated supply DIO (Diet Induced Obesity) studies Health monitoring Recovery of cryopreserved embryos Surgeries Benefits to Researchers in Europe and Asia The relationship between The Jackson Laboratory and Charles River provides researchers with the convenience of working with Charles River s numerous international sales offices, in their own time zones and in their native languages when ordering and importing JAX Mice strains. Through this cooperative agreement, the worldwide research community has more convenient access to JAX Mice and benefits from the expertise of both organisations. Importing JAX Mice strains Please contact us to request a JAX Mice order form. We are also pleased to assist customers with their search for a specific JAX Mice strain. Once you select a JAX Mice strain of interest, we can furnish you with an import price quotation - including details of availability. Charles River will take charge of all importation steps. Charles River will not be responsible for any damages arising during the importation process whilst the mice are in the care of non-charles River transport companies, e.g. airlines. For Technical Support Technical information is available by telephone : in France : +33 (0) in Germany : +49 (0)9761/ in U.K. : in Italy : or on the web at: and [email protected] Educational Information on Mouse Genetics and Strain Nomenclature Handbook on Genetically Standardized Mice See: JAX Mice Genetic Quality Control Programme. See: JAX Mice Genetic Stability Program. See: Interactive Tutorial on Mouse Strain Nomenclature. See: Published Reference: Taft RA, Davisson M, Wiles MV Know Thy Mouse. Trends Genet 22:

30 Inbred Mice 129 Mice 129S2/SvPasCrl FE Age in Weeks Price - Price ,18 30, ,54 32, ,80 34, ,13 37,13 Additional Week 2,40 2,40 ORIGIN The 129/Sv inbred strain genotype C-P (wild-type alleles at the albino and pink-eyed dilution loci) was established by Dr LC Stevens from The Jackson Laboratory. Because of his interest in testicular teratomas which are extremely frequent in the 129 inbred strain, he investigated the effect of certain mouse mutations, which affect the male germ line, on the frequency of these tumors. One of these mutations was steel (SI) which, at the heterozygous state, is responsible for a dilution of the coat color and a depigmentation of the tail tip. The original 129 inbred strain is homozygous for the two recessive mutations chinchilla (Tyr c-ch ) and pink-eyed dilution (p). Its coat color is cream. In order to distinguish the effect of the steel mutation on the coat color, Dr Stevens introduced by repeated backcrosses the wild-type alleles at the albino and pink-eyed dilution loci from the C3H/He inbred strain.this is the reason why the 129/Sv inbred strain, unlike other 129 strains, has an agouti coat color. Testicular teratomas have an incidence of approximately 1% as this strain does not carry the Dnd1 Ter mutation. In the seventies, Dr Stevens introduced the 129/Sv strain to the institut Pasteur in the Laboratory of Dr JL Guenet, where it has been maintained for over 20 years, Charles River France acquired this strain in August The strain was renamed 129S2 in 1999 after the revision of the international nomenclature. COAT COLOR Agouti JAX Mice Strain : BALB/cJ BALB/cJ FE Age in Days Price - Price ,52 9, ,29 11, ,16 12, ,53 13,53 Additional Week 2,10 2,10 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: White (albino). JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 26

31 Inbred Mice JAX Mice Strain: BALB/cByJ BALB/cByJ FE Age in Weeks Price - Price ,14 13, ,39 13, ,64 14, , ,97 17, ,16 20,16 Additional week 2,40 2,40 Retired breeder 11,16 Time mated females Enquire Female with litter Enquire Pregnant Enquire ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Albino. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. BALB/cAnNCrl Mice BALB/cAnNCrl FE Age in Weeks Price - Price ,28 11, ,85 11, ,70 12, ,81 13, ,49 14, ,39 15,39 Additional week 2,10 2,10 Retired breeder Enquire Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire ORIGIN H.J Bagg developed the Bagg albino in 1913 using stock from an Ohio pet dealer. Inbred in 1923 by McDowell. To Snell in 1932 at F26, to Andervont in To NIH at F72 in To Charles River USA from NIH in Caesarian derived in This strain has been very widely used for in vivo production of monoclonal antibodies by the ascites method because of its haplotype with many hybridoma cell lines (BALB/c mouse melanoma [NS1] fusion products). This mouse is also used frequently for imunisation and B-cell collection. Low incidence of mammary tumors (10-20%). Arteriosclerosis common in both sexes. Male aggression is frequently overestimated. HAPLOTYPE H-2 d. COAT COLOR Albino. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 27

32 Inbred Mice JAX Mice Strain: C3H/HeOuJ C3H/HeOuJ FE Age in Weeks Price - Price ,22 15, ,70 16, ,59 17, ,42 19, ,25 21, ,10 23,10 Additional week 2,40 2,40 Retired breeder Enquire Enquire ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Agouti. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies C3H/HeNCrl Mice C3H/HeNCrl FE Age in Weeks Price - Price ,07 14, ,44 15, ,28 16, ,98 17, ,74 19, ,36 21,36 Additional week 1,95 1,95 Retired breeder 12,48 12,48 Female with litter (males and females) Enquire ORIGIN From a cross of a Bagg albino female and a DBA male by Strong in A litter of 4 females and 2 males sent to Andervont in 1930; then to Heston at F35. To NIH in 1951 from Heston at F57. To Charles River USA from NIH in Caesarian derived in % hepatomas at 14 months. This is an MMTV negative strain and hence does not show high incidence of mammary tumours. Resistant to Leishmania infection. High complement activity. Retinal degeneration allele (Pde6b, formely known as rd) is carried on chromosome 5. Mated females are highly susceptible (89%) to cardiac calcinosis. HAPLOTYPE H-2 k. COAT COLOR Agouti. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 28

33 Inbred Mice JAX Mice Strain: C57BL/6J C57BL/6J FE Age in Weeks Price - Price ,77 12, ,72 13, ,19 15, ,44 16, ,88 17, ,03 20,03 Additional week 2,40 2,40 Retired breeder 11,63 11,63 Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Black. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. C57BL/6NCrl Mice C57BL/6NCrl FE Age in Weeks Price - Price ,35 11, ,42 12, ,63 13, ,53 14, ,39 15, ,49 17,49 Additional week 2,30 2,30 Retired breeder 13,44 13,44 Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire ORIGIN Developed by C.C. Little in 1921, from a mating of Miss Abby Lathrop s stock that also gave rise to strains C57BR and C57L. To The Jackson Laboratory in 1948 from Hall. To NIH in 1951 from The Jackson Laboratory at F32. To Charles River in 1974 from NIH. Hysterectomy rederived in HAPLOTYPE H-2 b. COAT COLOR Black. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 29

34 Inbred Mice CBA Mice CBA/CaCrl FE Age in Days Price - Price - Up to 21 10,68 10, ,76 11, ,75 12, ,86 13, ,91 15, ,96 16, ,16 19,16 Additional week 2,10 2,10 Retired breeder Enquire 12,54 Littermates 21 days old 11,80 11,80 Non-Littermates 21 days old 11,80 11,80 Lactating mouse with litter 97,00 Time mated (over 14 day gestation) Enquire Untimed pregnant 73,54 Insert microchip 12,10 12, MEAN WEIGHT +/- 1 STANDARD DEVIATION FOR GUIDANCE ONLY FE ORIGIN From a cross of a Bagg albino female and a DBA male by Strong in The CBA strain was selected for a low mammary tumour incidence. Transferred via The Jackson Laboratory to Haldane and Gruneberg in 1932 To Carter (CBA/Ca) in The CBA/Ca is the substrain most commonly used in British research. VAF Plus breed stock to Charles River UK from Glaxo in Absence of lower third molars in about 18%, few skeletal variants, some mammary tumours in breeders. Do not develop antinuclear antibodies or LE cells with aging. HISTOCOMPATIBILITY H-1 a, H-2 k, H-3. COAT COLOR Agouti. JAX Mice Strain: CBA/J CBA/J FE Age in Weeks Price - Price ,86 15, ,12 17, ,77 19, ,44 22, ,07 25, ,77 27,77 Additional week 2,30 2,30 Retired breeder 13,59 13,59 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Agouti. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 30

35 Inbred Mice JAX Mice Strain: DBA/1J DBA/1J FE Age in Days Price - Price - up to 21 17,89 17, ,40 18, ,15 21, ,93 23, ,39 26, ,24 29, ,11 32,11 Additional week 2,90 2,90 Pregnant Enquire Retired breeder 15,73 15,73 Insert Microchip 14,02 14,02 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Non-agouti dilute brown. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. Data derived from Charles River weight studies JAX Mice Strain: DBA/2J DBA/2J ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Non-agouti dilute brown. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. DBA/2NCrl Mice DBA/2NCrl FE Age in Weeks Price - Price ,84 17, ,84 17, ,01 20, ,33 21, ,23 22, , Additional week 2,10 2,10 Retired breeder 13,73 13,73 Female with litter (males and females) Enquire FE Age in Weeks Price - Price ,05 16, ,98 17, ,13 19, ,00 20, ,77 20,77 Additional week 2,10 2,10 Retired breeder 13,37 ORIGIN Developed by C.C. Little in 1909 from stock segregating for coat color. Oldest of all the inbred strains of mice. In crosses were made between sublines, and several new sublines were established, including the widely used sublines 1 (previously called 12) and 2 (previously called 212). To Mider in To NIH in 1951 from Mider at F34. To Charles River in 1974 from NIH. Hysterectomy rederived in HAPLOTYPE H-2 d. COAT COLOR Non-agouti dilute brown Data derived from Charles River weight studies J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 31

36 Inbred Mice FVB Mice FVB/NCrl Individual shipment of males after 9 weeks. FE Age in Weeks Price - Price ,15 11, ,20 12, ,95 13, ,93 15, ,57 17, ,99 20,99 Additional week 2,10 2,10 ORIGIN Derived in 1935 from an outbred Swiss colony [N.GP(S)] at NIH. During the early 1970 s, established as an inbred strain called Fv1b (sensitive to the B strain of Friend leukemia) at NIH. To Charles River from NIH in Caesarean derived in HAPLOTYPE H-2 q. COAT COLOR Albino. JAX Mice Strain: SJL/J Mice SJL/J FE Age in Weeks Price - Price ,82 18, ,78 19, ,99 21, ,33 24, ,51 26,51 Additional week 2,30 2,30 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Albino. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Significant degree of fighting in mice housed together. Individually housing after weaning is recommended. Individual shipment of males after 6 weeks. Individual shipment of females after 8 weeks. Data derived from Charles River weight studies B6 albino Mice B6N-Tyr c /BrdCrCrl FE Age in Weeks Price - Price ,74 20, ,63 21, ,58 22, ,41 24, ,25 26,25 ORIGIN Received by NCI from Dr. Allan Bradley at Baylor College of Medicine in The B6 albino strain is a spontaneous albino mutant coisogenic C57BL/6 strain. The mice contain a mutation in the tyrosinase gene, and when homozygous for the mutation the coat color of the mice is albino rather than black. To Charles River US in 2009 from NCI. To Charles River France in COAT COLOR White (Albino). RESEARCH APLICATION creation of chimeras with B6N-derived embryonic stem cells MHC HAPLOTYPE H2b. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 32

37 Hybrid Mice JAX Mice Strain: B6CBAF1/J Mice B6CBAF1/J FE Age In Weeks Price - Price ,84 14, ,99 14, ,40 16, ,20 19,20 Additional week 2,10 2,10 ORIGIN: First generation (F1) progeny of a cross between female JAX Mice strain C57BL/6J and male JAX Mice strain CBA/J. Both parental strains are maintained in breeding colonies derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Agouti. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies B6C3F1/Crl Mice B6C3F1/Crl FE Age in Weeks Price - Price ,47 13, ,10 14, ,73 14, ,35 15,35 Pregnant / time mated females Enquire Female with litter (males and females) Enquire ORIGIN Mice result from a cross between female C57BL/6NCrl and male C3H/He mice. Contact your local office (see page 6) for additional information. COAT COLOR Agouti. B6D2F1/Crl Mice B6D2F1/NCrl ORIGIN Mice result from a cross between female C57BL/6NCrl and male DBA/2NCrl mice. COAT COLOR Black. Contact your local office (see page 6) for additional information FE Age in Weeks Price - Price ,24 11, ,91 11, ,71 12, ,43 13,43 Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 33

38 Hybrid Mice JAX Mice Strain: B6D2F1/J B6D2F1/J FE Age In Weeks Price - Price ,84 12, ,96 12, ,91 13, ,04 15,04 Additional week 2,10 2,10 ORIGIN: First generation (F1) progeny of a cross between female JAX Mice strain C57BL/6J and male JAX Mice strain DBA/2J. Both parental strains are maintained in breeding colonies derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Black. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies CB6F1/Crl CB6F1/Crl ORIGIN First generation (F1) of a cross between a female BALB/cAnN x male C57BL/6N. COAT COLOR Agouti. FE Age In Weeks Price - Price ,16 13, ,86 14, ,66 15, ,46 16,46 Time mated females Enquire Female with litter (males and females) Enquire Pregnant Enquire CD2F1/Crl Mice CD2F1/Crl FE Weight in Grams Price - Price ,05 14, ,36 15, ,78 16, ,99 17,99 ORIGIN First generation (F1) progeny of a cross between female BALB/cAnNCrl x male DBA/2NCrl. COAT COLOR Brown agouti. Additional Hybrid Mice NMRCF1/Crl ORIGIN The hybrid NMRCF1/Crl mouse is a result from a cross between a Crl:NMRI female and a JAX Mice Strain BALB/cByJ male. COAT COLOR Albino. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 34

39 Disease and Translational Models METABOLIC, RENAL AND CARDIOVASCULAR MODELS THE POUND MOUSE C57BL/6NCrl-Lepr db-lb /Crl OBESE LEAN Age in Weeks Price - Price Consult us Consult us 6 Additional week ORIGIN This model was isolated from a C57BL/6NCrl colony in a Charles River barrier facility in the United States in The mutation is a deletion/inversion event in exon of the leptin receptor gene. Lack of leptin receptor protein. DNA sequence analysis of the leptin receptor gene has revealed that exon 2 is deleted, likely resulting in complete lack of the leptin receptor protein in this line. Homozygotes are infertile and the strain is maintained by heteroygotes mating. COAT COLOR Black It is a condition of sale that customers (or their employees) purchasing or receiving The Pound Mouse are not permitted to breed or cross breed The Pound Mouse without the prior written approval of Charles River. JAX Mice Strain: Obese Mice ob/ob B6.V-Lep ob /J FE Age in Weeks Price - Price ,15 130, ,52 133, ,57 137,57 Additional week 6,36 6,36 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Black. CONTROL: Heterozygote or wild type from the colony or C57BL/6J. DIET: 5K20 or equivalent. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies JAX Mice Strain: Diabetic Mice db/db BKS.Cg-Dock7 m +/+Lepr db /J FE Age in Weeks Price - Price ,58 112, ,26 116, ,68 119, ,30 123,30 Additional week 6,36 6,36 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Black. CONTROL: Heterozygote from the colony. DIET: 5K52 or equivalent JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 35

40 Disease and Translational Models JAX Mice Strain: ApoE Mice B6.129P2-Apoe tm1unc /J FE Age in Weeks Price - Price ,40 126, ,41 129, ,28 132, ,42 135, ,43 138,43 Additional week 5,75 5,75 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Black. CONTROL: JAX Mice Strain: C57BL/6J. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. Data derived from Charles River weight studies JAX Mice Strain: NOD Mice NOD/ShiLtJ FE Age in Weeks Price - Price ,74 50, ,05 57, ,59 64, ,90 70, ,07 77,07 Additional week 6,66 6,66 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: White (Albino). JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. Additional Models Available from The Jackson Laboratory Many additional mouse models supporting metabolic and cardiovascular disease research are available from The Jackson Laboratory and may be obtained by importation through Charles River. Charles River serves as the exclusive European commercial distributor of The Jackson Laboratory's JAX Mice strains. Cryopreserved Models The strains listed below are currently maintained as frozen embryos. Two breeding pairs can be made available upon request approximately 12 weeks after order receipt. A dedicated supply can also be established for larger order requests. Please contact Customer Service for pricing and availability. COMMON NAME NOMENCLATURE SPECIES COAT COLOR 11BHSD2* C57BL/6NCrl-Tg(aMhc-Hsd11b2) Mouse Black GLUT 4* C57BL/KsJ-db/db-Tg(SLC2a4)1Jdm Mouse Black GSK3B* FVB/N-Tg(Mic2-tTA-GSK3) Mouse White HSD11B1* FVB/N-Tg(AP2-HSD11b1) Mouse White LCAT* C57BL/6J-Tg(Alb-LCAT)1Jdm Mouse Black LOX-1* C57/BL6J-Tg(OLR1) Mouse Black PCSK9* C57BL/6J-Tg(ALB-PCSK9) Mouse Black Rip-HAT* FVB/N-Tg(Ins2-IAPP)RHF Soel Mouse White *These models may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 36

41 Disease and Translational Models INFLAMMATION & IMMUNOLOGY MODELS Ly5.1 Mice B6.SJL-Ptprc a Pepc b /BoyCrl / FE Age in Weeks Price ,88 Additional Week 3,50 ORIGIN The strain was originally developed at the Sloan Kettering Institute where it was backcrossed on a non-specified C57BL/6 strain. The congenic strain "C57BL/6-Ly5.1" carries the allele of the SJL mouse in the Ptprc gene locus: "Ptprc a " or "CD45.1" or "Ly5.1". Charles River Europe breeds CD45.1 expressing B6.SJL-Ptprc a Pepc b /BoyCrl mice in Italy. OT I C57BL/6-Tg(TcraTcrb)1100Mjb/Crl / FE Age in Weeks Price ,30 Additional Week 3,50 ORIGIN From the Walter and Eliza Hall Institute, Victoria, Australia, to Charles River France in These homozygous mice contain transgenic inserts for mouse Tcra-V2 and Tcrb-V5 genes. The transgenic T cell receptor was designed to recognize ovalbumin residues in the context of H2Kb and used to study the role of peptides in positive selection and the response of CD8+ T cells to antigen. Like most TCR transgenics, these mice are somewhat immunodeficient. OT II C57BL/6-Tg(TcraTcrb)425Cbn/Crl / FE Age in Weeks Price ,30 Additional Week 3,50 ORIGIN From the Walter and Eliza Hall Institute, Victoria, Australia, to Charles River France in These homozygous transgenic mice express the mouse alpha-chain and beta-chain T cell receptor that pairs with the CD4 coreceptor and is specific for chicken ovalbumin in the context of I-A b. Homozygous mice are viable and fertile. In these mice there is a four-fold increase in the CD4 to CD8 peripheral T cell ratio, and lymph node T cells demonstrate a dose-dependent proliferative response to the specific ovalbumin ligand. These transgenic mice are useful for studying in vivo T cell biology such as TCR-ligand interactions, T cell activation, thymic selection, cross-presentation of antigens, process of thymic selection and central and peripheral T cell tolerance and induction. Foxp3-IRES-mRFP (FIR) Mice NOMENCLATURE C57BL/6J-Foxp3 tm1flv /Crl ORIGIN This strain was created in the laboratory of Dr. Richard A. Flavell, Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, United States of America. The Foxp3-IRES-mRFP (FIR) mouse model displays a normal expression of the endogenous Foxp3 gene and an intact function of regulatory T cells. Monitoring of regulatory T cell trafficking and cell sorting is achieved through the mrfp expression detection. For any requests and orders, please contact: [email protected] IL-4-IRES-eGFP (4get) Mice NOMENCLATURE C.129X1-Il4 tm1lky and B6.129X1-Il4 tm1lky /Crl ORIGIN This strain was created in the laboratory of Pr. Richard Locksley, Department of Infectious Disease, University of California San Francisco- HHMI, United States of America. The IL-4-IRES-eGFP (4get) reporter mouse displays a normal expression of the endogenous IL-4 gene and an intact function of effector T cells. Monitoring of IL-4-expressing cell trafficking and sorting is achieved through the egfp expression detection. For any requests and orders, please contact: [email protected] 37

42 Disease and Translational Models JAX Mice Strain DBA/1J NOMENCLATURE DBA/1J See page 31. Research Applications: This strain is widely used as a model for collagen-induced rheumatoid arthritis. See : askforthej.org/jaxmice/ The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. Additional Models Available from The Jackson Laboratory Many additional inflammation and immunology mouse models are available from The Jackson Laboratory and may be obtained by importation through Charles River. Charles River serves as the exclusive European commercial distributor of The Jackson Laboratory's JAX Mice strains. Cryopreserved Model Maintained as frozen embryos. Two breeding pairs can be made available upon request approximately 12 weeks after order receipt. A dedicated supply can also be established for larger order requests. Please contact Customer Service for pricing and availability. COMMON NAME NOMENCLATURE SPECIES COAT COLOR MMP9* FVB/N-Tg(Eno2-MMP9) Mouse White * This model may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc. ONCOLOGY MODELS P110 Ludwig Mice Limited availability, upon reservation from Charles River USA. JAX Mice strain: NOD scid gamma (NSG) Mice NOD.Cg-Prkdc scid Il2 rgtm1wjl /SzJ. See askforthej.org/jaxmice/ See page 41. CENTRAL NERVOUS SYSTEM (CNS) MODELS PGP Mice NOMENCLATURE Crl:CF1-Abcb1a mds Limited availability, upon reservation from Charles River USA. Cryopreserved Model Maintained as frozen embryos. Two breeding pairs can be made available upon request approximately 12 weeks after order receipt. A dedicated supply can also be established for larger order requests. Please contact Customer Service for pricing and availability. COMMON NAME NOMENCLATURE SPECIES COAT COLOR NSE-p25* FVB/N-Tg(Eno2-CDKSr1)1Jdm Mouse White * This model may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc. Additional Models Available from The Jackson Laboratory Many additional CNS models are available from The Jackson Laboratory and may be obtained by importation through Charles River. Charles River serves as the exclusive European commercial distributor of The Jackson Laboratory's JAX Mice strains. Dedicated Supply of JAX Mice As a result of the collaborative agreement between The Jackson Laboratory and Charles River, Charles River s European facilities are able to offer you dedicated supplies of certain JAX Mice strains that are typically only available as imported strains. Contact your local office (see page 6) for additional information. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 38

43 Immunodefi cient Models Immunodefi cient Models Oncology is one of the leading areas of research into new therapeutics. Charles River s global portfolio of high-quality immunodefi cient models gives you the benefi t of partnering with an industry leader offering an infrastructure capable of advancing your research now and in the future.

44 Immunodefi cient Models Common Name Nomenclature Page Nude Mice Crl:CD1-Foxn1 nu 39 Nude Mice Crl:NU(Ico)-Foxn1 nu 39 BALB/c-Nude Mice CAnN.Cg-Foxn1 nu /Crl 39 BALB/c-Nude Mice* CByJ.Cg-Foxn1 nu /J 39 SCID Mice CB17/lcr-Prkdc scid /lcrlcocrl 40 SHO Mice Crl:SHO-Prkdc scid Hr hr 40 SCID Beige Mice CB17.Cg-Prkdc scid Lyst bg-j /Crl 40 NOD SCID Mice* NOD.CB17-Prkdc scid /J 41 NSG Mice* NOD.Cg-Prkdc scid Il2rg tm1wjl /SzJ 41 Nude Rats Crl:NIH-Foxn1 rnu 42 NIH-III Mouse Crl:NIH-Lyst bg Foxn1 nu Btk xid 42 NU/NU Mouse Crl:NU-Foxn1 nu 42 NMRI-nude Crl:NMRI-Foxn1 nu 42 SHC Mice CB17.Cg-Prkdc scid Hr hr /IcrCrl 42 Athymic Nude Mice Crl:NU(NCr)-Foxn1 nu 42 * JAX Mice strains. Immunodefi cient Models

45 Immunodeficient Models Strain Species Hair T cells B Cells NK Cells CD1-Nude (Outbred) Mouse NO NO YES YES Nu/Nu Nude (Outbred) Mouse NO NO YES YES BALB/c Nude* Mouse NO NO YES YES NIH III Nude (Outbred) Mouse NO NO NO Impaired C.B-17 SCID Mouse YES NO NO YES ICR Outbred SCID Mouse YES NO NO YES SHO (SCID Hairless Outbred) Mouse NO NO NO YES SHC (SCID Hairless Congenic) Mouse NO NO NO YES SCID - Beige (Congenic) Mouse YES NO NO Impaired NOD.SCID (Congenic)* Mouse YES NO NO Impaired Nu/Nu (Outbred) Rat NO NO YES YES NOD scid gamma (NSG)* Mouse YES NO NO NO * JAX Mice Strains Nude Mice Crl:CD1-Foxn1 nu Crl:NU(Ico)-Foxn1 nu Crl:NU(Ico)-Fox1 nu Crl:CD1-Fox1 nu /FE /FE Age in Weeks Price - Price - Homozygous nu/nu 4 46,04 46, ,97 51, ,10 57, ,23 62, ,36 67,36 Additional week 3,47 3,47 Heterozygous nu/+ 4 weeks 23,65 23, NOMENCLATURE Crl:CD1-Foxn1 nu ORIGIN Developed from the transfer of the nude gene to a CD-1 mouse through a series of crosses and back-crosses, beginning in 1979 at Charles River, Wilmington, MA. The animal does not have a thymus and is therefore unable to produce T-cells and is consequently immunodeficient. COAT COLOR Homozygotes: hairless, unpigmented. Heterozygotes: haired, albino. BREEDING LOCATION Germany, USA, UK, Italy. NOMENCLATURE Crl:NU(Ico)-Foxn1 nu ORIGIN The mutation ocurred in 1962, in a colony of albino outbred mice maintained at the Ruchill Hospital in Glasgow. In 1966, Flanagan gave the first detailed description of this mutant. It was not until 1968, however, that it was first noticed that the thymus was missing (Pantelouris EM). These nude mice originate from the Swiss strain. In 1974, The Gustave Roussy Institute (Villejuif, France) obtained the mice from Dr Carl Hansen s department at the NIH, Bethesda, MD, USA. The first pairs were introduced into Charles River France in COAT COLOR Homozygotes: hairless, unpigmented. Heterozygotes: haired, albino. BREEDING LOCATION France Strain: Crl:CD1-Fox1 nu 12 BALB/c-Nude Mice CAnN.Cg-Foxn1 nu /Crl JAX Mice Strain: CByJ.Cg-Foxn1 nu /J CAnN.Cg-Foxn1 nu /Crl CByJ.Cg-Foxn1 nu /J /FE /FE Age in Weeks Price - Price - Homozygous nu/nu 4 80,18 80, ,01 83, ,61 87, ,12 91, ,76 93,76 Additional week 4,05 4,05 Heterozygous nu/+ 4 weeks 49,09 49,09 NOMENCLATURE CAnN.Cg-Foxn1 nu /Crl ORIGIN Developed through crosses and backcrosses between BALB/cABom-nu and BALB/cAnNCrj-nu at Charles River Japan (CRJ). Pedigreed pregnant females of BALB/cAnNCrjnu were received from CRJ in This mouse is inbred, and genetic monitoring results confirm it to be a BALB/c nude. It also lacks a thymus and is therefore T-cell deficient. BREEDING LOCATION Germany, USA, UK. COAT COLOR Homozygotes: hairless, unpigmented. Heterozygotes: haired, albino. NOMENCLATURE CByJ.Cg-Foxn1 nu /J ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. BREEDING LOCATION France. COAT COLOR: Homozygotes: hairless, unpigmented. Heterozygotes: haired, albino. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies Strain: CByJ.Cg-Foxn1 nu /J J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 39

46 Immunodeficient Models SCID Mice CB17/Icr-Prkdc scid /IcrIcoCrl FE Age in Weeks Price - Price ,81 63, ,71 65, ,69 67, ,02 70, ,05 73,05 Additional week 3,77 3,77 ORIGIN The scid autosomal recessive mutation, was detected in 1980 by MJ Bosma and his group in an inbred strain (C.BKa-Igh b /Icr also known as C.B-17) of specific pathogen free mice at the Fox Chase Cancer Center, Philadelphia, PA, USA. Mice homozygous for the scid mutation, hereafter designated SCID mice, were established as a coisogenic partner strain of the normal C.B-17 strain. In 1989, Charles River France obtained SCID mice under licence from FCCC. COAT COLOR Albino. SCID Hairless Outbred Mice (SHO) Crl:SHO-Prkdc scid Hr hr FE Age in Weeks Price - Price ,59 69, ,67 71, ,82 73, ,37 76, ,68 79,68 ORIGIN The hairless SCID mouse was produced by Charles River Research Models in 2007 by inter-crossing the Crl:Ha-Prkdc scid and Crl:SKH1-Hr hr stocks. The resulting animals are homozygous for the Prkd cscid and the Hr hr mutations and thus exhibit the severe combined immunodeficiency phenotype characteristic of SCID mice and are also hairless. COAT COLOR Hairless, albino background. It is a condition of sale that customers (or their employees) purchasing or receiving SHO mice are not permitted to breed or cross breed SHO mice without the prior written approval of Charles River. SCID Beige CB17.Cg-Prkdc scid Lyst bg-j /Crl FE Age in Weeks Price - Price ,59 69, ,67 71, ,82 73, ,37 76, ,68 79,68 ORIGIN A congenic mouse that possesses both genetic autosomal recessive mutations SCID and beige. This mouse was developed by Croy, et al. at the University of Guelph by an intercross of C.B-17 SCID/SCID to C57BL/6 bg/bg mice. To Charles River USA in 1993 and to Charles River Germany in COAT COLOR White (Albino). 40

47 Immunodeficient Models JAX Mice Strain: NOD SCID NOD.CB17-Prkdc scid /J FE Age in Weeks Price - Price ,83 115, ,83 115, ,07 120, ,19 124, ,44 128,44 Additional week 4,02 4,02 ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOR: Albino. JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ The Jackson Laboratory s Genetic Stability Program is covered by 2010 US Patent 7,592,501 and 2012 US patent 8,110,721. Data derived from Charles River weight studies JAX Mice strain: NOD scid gamma (NSG) Mice NOD.Cg-Prkdc scid Il2rg tm1wjl /SzJ The prices shown below apply to non-profit users. For-profit customers should contact a local Charles River office for pricing options. Use of this strain requires execution of a material transfer agreement for non-profit users. Use of this strain by for-profit users requires execution of a license agreement. NOT-FOR-PROFIT USER PRICES S & FES Age in Weeks Price , , , , , ,36 > 10 Enquire Breeder pair Enquire Time Mated/Pregnant Females Enquire ORIGIN: The breeding colony for this strain is derived from and systematically reinfused with pedigreed JAX Mice stock obtained from The Jackson Laboratory. Charles River adheres to The Jackson Laboratory s breeding protocols and genetic quality program to maintain this breeding colony. Mice from this colony are genetically equivalent to those bred by The Jackson Laboratory and are considered authentic JAX Mice strains which are designated with a J as the final letter in the strain nomenclature. JAX Mice Strains are for internal research use only and should not be propagated for distribution or sale. COAT COLOUR: White (albino). JAX MICE STOCK NUMBER: STRAIN CHARACTERISTICS: For comprehensive strain information, see the strain data sheet at askforthej.org/jaxmice/ For physiological strain data, see Mouse Phenome Database at askforthej.org/mpd/ Data derived from Charles River weight studies J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 41

48 Immunodeficient Models Nude Rats Crl:NIH-Foxn1 rnu FE Age in Weeks Price - Price ,06 95, ,09 111, ,07 127, ,26 145,26 Additional week 15,06 15,06 ORIGIN The NIH nude rat was developed in 1979/80 through a series of matings involving 8 inbred rat strains. To Charles River USA from the NIH Animal Genetic Resources. Caesarian derived in This athymic model shows depleted cell populations in thymus-dependant areas of peripheral lymphoid organs. COAT COLOR Homozygotes: White, black or black and white, hairless. Heterozygotes: White, black or black and white, haired. Other Immunodeficient Models available from Charles River NIH-III Mouse NOMENCLATURE Crl:NIH-Lyst bg Foxn1 nu Btk xid NU/NU mouse NOMENCLATURE Crl:NU-Foxn1 nu NMRI-nude NOMENCLATURE Crl:NMRI-Foxn1 nu SCID Hairless Congenic (SHC) Mice NOMENCLATURE CB17.Cg-Prkdc scid Hr hr /IcrCrl Athymic Nude Mice NOMENCLATURE Crl:NU(NCr)-Foxn1 nu NOD SCID Mouse NOMENCLATURE NOD.C.B.17-Prkdc scid /IcrCrl Immunodeficient Models Available from The Jackson Laboratory Many additional immunodeficient mouse models are available from The Jackson Laboratory and may be obtained by importation through Charles River. Charles River serves as the exclusive European commercial distributor of The Jackson Laboratory's JAX Mice strains. Dedicated Supply of JAX Mice As a result of the collaborative agreement between The Jackson Laboratory and Charles River, Charles River s European facilities are able to offer you dedicated supplies of certain JAX Mice strains that are typically only available as imported strains. Contact your local office (see page 6) for additional information. J and JAX are a trademarks of The Jackson Laboratory registered in the United States. All rights reserved. 42

49 Hamster, Gerbil, Guinea Pig, Rabbit Because most diseases cause a wide range of complications, their study is complex and often requires research programmes to take a multidisciplinary approach. Therefore, aside from mouse and rat models, we also provide other species of research models in order to support your programme requirements. Hamster, Gerbil, Guinea Pig, Rabbit

50 Hamster, Gerbil, Guinea Pig, Rabbit Common Name Nomenclature Page New Zealand White Crl:KBL(NZW) 43 Dunkin Hartley Crl:HA 43 Hairless Guinea Pigs Crl:HA-Hr hr 43 Syrian Hamsters Crl:LVG(SYR) 44 Gerbils Crl:MON(Tum) 44 Hamster, Gerbil, Guinea Pig, Rabbit

51 Rabbits / Guinea Pigs New Zealand White Crl:KBL(NZW) ORIGIN To Charles River Canada in 1991 from Kitayama Breeding Laboratories, Japan. COAT COLOR Albino. FE Weight in Grams Price - Price - Up to ,67 100, ,48 120, ,43 154,43 > Enquire Enquire Retired breeder Enquire Time mated Enquire Pregnant Enquire Dunkin Hartley - Guinea Pigs Crl:HA FE Weight in Grams Price - Price - Up to ,26 48, ,52 52, ,45 58, ,43 63, ,64 68, Enquire Enquire NOMENCLATURE Crl: HA ORIGIN To Charles River in 1968 from Medical Research Council, Mill Hill. Caesarian derived in COAT COLOR Albino Cancellation fees may apply - consult us Additional Model Hairless Guinea Pig NOMENCLATURE Crl:HA-Hr hr Limited availability, upon reservation from Charles River USA. Custom breeding of GM rabbits available on request. Please consult us Orders for rabbits: cancellation fees may apply - consult us. 43

52 Hamsters / Gerbils Syrian Hamsters - Hamsters Crl:LVG(SYR) FE Age in Weeks Price - Price ,82 26, ,46 31, ,20 31, ,70 36, ,70 40, ,70 40,70 ORIGIN Three members of a litter captured in Syria in 1930 were retained in captivity. It is the progeny of these animals that were first imported to the United States in Descended from two original colonies acquired by Lakeview in 1949 and Closed outbred colony since To Charles River Germany from Charles River Canada in COAT COLOR Medium tan Gerbils Crl:MON(Tum) FE Weight in Grams Price - Price - < 30 42,87 42, ,90 43, ,61 48, Enquire Enquire ORIGIN The stock was obtained from Tumblebrook Farms in Rederived in COAT COLOR predominantly agouti with some black. 44

53 Preconditioning Services, Surgery and Contract Services Preconditioning Services, Surgery and Contract Services Our services can help alleviate the space, time and labour costs involved with refi ning a model to meet your unique research requirements. Whether you are looking for animals fed a special diet, or reared to a certain age, or sugically modifi ed, Charles River has stateof-the-art animal facilities, professional animal care and robust model selection to deliver study-ready animals right to your door.

54 Preconditioning Services, Surgery and Contract Services Preconditioning Services Preconditioning Services (page 45) Charles River offers a fl exible range of preconditioning services including model aging programmes and diet inductions. During the preconditioning period, various phenotypic parameters can be measured and recorded on an as-needed basis. In addition, surgical manipulation can be performed on the animals as part of the preconditioning process. Surgical Services (pages 46-47) We offer a variety of surgical services, including vascular and non vascular catheterisations; device implants; and soft tissue, neurological and cardiovascular procedures, on various species rat, mouse, Guinea pig in our European dedicated production facilities. Our surgical procedures are developed in-house and subject to review and approval by our Ethics committee. Our biosecurity measures include barrier-type surgical suites, use of dedicated laminar fl ow workstations by each surgeon and housing of animals in adapted caging systems during the animals stay in surgery. Surgical Support The Rent-a-Surgeon programme allows one of our surgical technicians or veterinarians to travel to your facility for an entire day or more to perform surgical procedures as requested by you. Please note that the Rent-a-Surgeon service is also available for large animal surgeries. The Rent-a-Trainer programme provides a full day or more of on-site surgical training on approved procedures for your staff. Biospecimens (page 48) Charles River can provide rat, mouse, guinea pig, hamster or gerbil biospecimens (tissues, organs, blood products) upon request. Biospecimens are collected and processed in our dedicated facilities by experienced technicians. Antibody Production Protocols (page 49) Charles River serves as a fl exible and reactive partner for conducting your immunisation protocols on a wide range of species from SPF rodents to large animals. ALZET Osmotic Pumps (pages 50-51) ALZET osmotic pumps are miniature infusion systems that deliver test agents at controlled rates into mice, rats and other laboratory animals. Charles River is the exclusive distributor for Europe. Biological and Quality Control Testing (pages 52-53) Charles River offers a set of tests conducted in compliance with Good Manufacturing Practices in our Pharmaceutical Facility: sample preparation, In vivo pyrogen testing, abnormal toxicity tests, safety tests, systemic injection tests, biological activity testing Contact us: [email protected]

55 Preconditioning Services PRECONDITIONING SERVICES Charles River Preconditioning Services allow researchers to save valuable resources by purchasing animals ready to use for your research. Charles River offer preconditioning studies from standardised to highly individualised protocols to suit your requirements. For further information or a quotation, please contact our technical services team. Feeding Studies / Surgical and Chemical Manipulations Charles River offers customised preconditioned models in accordance with the objectives/requirements of your experiments. Models can be pre-fed with special diets to induce obesity, hypertension, stroke or other conditions. Our team can advise you on the selection of the appropriate diet depending on the model. Charles River offers specific disease induction by injection or irradiation (e.g. diabetes induced by streptozotocin injection, pristanisation ). Physiological modifications or specific diseases can be induced by surgical manipulation upon request, see page 46. Aging Studies In some models, disease conditions develop only as the animal ages. Charles River can hold and care for the animals in a barriered preconditioning room and deliver them to you as needed. In addition, Charles River also offer off the shelf aged models. Please enquire with Customer Services for availability. Aged Animals JAX Mice strain C57BL/6J Crl:OFA(SD) Crl:WI(Han) Age Up to 15 months Up to 15 months Up to 15 months Therapeutic Field Induced Model Surgically Induced Model Contract Research Service Metabolic and Cardiovascular Type 1 or 2 Diabetes Left Coronary Artery Ligation Custom Diet Administration (Rat / Mouse) (Myocardial infarction) High Fat / Energy Diet Diet Induced Obesity Models Ischemia/perfusion Cholesterol Diet C57BL/6 DIO Mouse Cafeteria Diet CD DIO Rat Organ / Tissue Collection Obese Prone Rat STZ Injection Nephropathy and Hypertension Diet Induced Models Renal Failure Model Custom Diet Administration Dahl/Salt Sensitive Rat (Unilateral or 5/6 Nephrectomy) High Salt Diet Stroke Prone Rat Ischemia/perfusion Organ/Tissue Collection Gerontology and Aged Animals Parkinson s Model Custom Ageing Neurodegeneration (6-OH Induction) Organ / Tissue Collection Alzheimer s Model Histopathology ALZET osmotic pump implantation Brain canulation Endocrinology Aged Animals Ovariectomy Custom Ageing Hysterectomy / Castration Custom Diet Administration ALZET osmotic Pump Compound Administration Implantation - Pellets ADME & PK Vascular Catheterizations Compound Administration Non Vascular Catheterizations Intermediate / End Point Blood Sampling Clinical Observation Organ collection 45

56 Surgery Services SURGERY SERVICES Charles River offers a variety of surgical services on three species - rats, mice and guinea pigs - at our various locations across Europe. Our surgical procedures are developed in-house and subject to approval by our ethics committee. The procedures are performed by trained surgical technicians under the supervision of veterinary staff, with regular quality control checks. Prices apply for surgical procedures on juvenile and adult CD rats, OFA, rats, Wistar Han rats, CD1 mice, NMRI mice and OF1 mice. Animals, crates transport gel and transportation are not included in the price. In addition, importation costs may apply for the strains that are not bred at your local Charles River facility. Contact us for additional information. In order to fully monitor the successful recovery of animals from surgery, we allow sufficient time for recovery before shipping. Vascular Catheters (1) Weight Rats Mice Guinea Pigs Carotid artery > 25 g mice > 150 g rat 107,15 134,50 - Femoral artery > 200 g 117, Jugular vein > 25 g mice 94,25 137,10 137,10 Jugular vein connected to harness > 100 g rat Enquire Enquire Enquire Femoral vein > 100 g 119, Portal vein (through mesenteric vein) > 250 g 180, Double jugular vein > 150 g 153, Carotid artery and jugular vein > 150 g 203, Femoral artery and femoral vein > 200 g 232, Jugular vein and femoral vein > 100 g 210, Portal vein and jugular vein > 250 g 270, Femoral vein connected to harness > 100 g 181, Jugular vein and femoral vein connected to a double harness > 100 g 305, (1) Prices given are for standard polyurethane catheters. Other types of catheter are available on request. Contact us for additional information. Non-Vascular Catheters (1) Weight Rats Mice Guinea Pigs Bile duct (connected to the duodenum) > 250 g 219, Bile duct connected to a double harness > 250 g 361,05 Duodenal catheter* > 150 g 170, Stomach catheter* > 150 g 145, (1) Prices for standard Polyurethane catheters. Other types of catheters are available on request, contact us for additional information. * Infusion only. Excision Surgery Age/ Weight Rats Mice Guinea Pigs Hypophysectomy* > 4 weeks 41, Orchidectomy (castration) > 3 weeks 23,35 23,40 23,40 Ovariectomy > 3 weeks 33,85 33,90 33,90 Splenectomy 5-6 weeks 45,85 45,90 Adrenalectomy 5-6 weeks 45,85 45,90 - Thyro-parathyroidectomy 5-6 weeks 56, Thymectomy > 200 g 128, Vasectomy > 3 weeks 31,85 31,85 - Thyroidectomy with parathyroid implant 5-6 weeks 64, Parathyroidectomy 5-6 weeks 64, Partial hepatectomy (70%) 8 weeks 132, * Price for OFA Rats. Other strains: please consult us. Disease models Weight Rats Mice Guinea Pigs Myocardial infarction (left coronary artery ligation)* > 28 g Enquire 330,60 - Unilateral nephrectomy > g 46,75 46,75 46,75 Nephrectomy 5/6 > 150 g 105, Nephrectomy 2/6 > 150 g 46, Parkinson's disease (chemical induction) > 225 g 243, Arthritis (Freund Adjuvant)* > 140 g 40, Arthritis (Monoiodoacetate Sodium)* > 125 g 46, * Performed only on specific strains. Contact us. 46

57 Surgery Services Neurological Procedures Weight Rats Mice Guinea Pigs Intralateral brain cannulation (1) > 175 g 202,50 230,40 - Double intralateral ventricle cannulation (1) > 175 g 213, rd ventricle cannulation > 175 g 202, Unilateral ventricle cannulation (1) > 175 g 213,30 230,40 - Bilateral subdiaphragmatic vagotomy > 175 g 125, Intrathecal Catheter (1) > 175 g 199, Intracisternal Catheter > 175 g 199, (1) For infusion only; no sample collection. Device Implantations (1) Age/Weight Rats Mice Guinea Pigs ALZET osmotic pumps - Connected to a catheter > 3 weeks 45,75 45, Connected to a BIK > 3 weeks 58,55 58, Subcutaneous 43,10 43, Intraperitoneal 58,00 58,00 - Electrocardiogram sensor (ECG) > 225 g 134,55 Enquire - Electroencephalogram sensor (EEG) > 200 g 147, Electromyogram sensor (EMG) > 200 g 115, Blood pressure sensor (BP) > 200 g 167, Blood pressure + Electrocardiogram sensor (BP + ECG) > 200 g 198, Temperature sensor > 200 g 115,80 115,80 - Electromyogram + Electroencephalogram sensor (EMG + EEG) > 200 g 262, (1) Price of implants is not included in the price of the surgical procedure. Telemetry implants are to be provided by the customer. Training Customized Training Sessions : Charles River offers specific training programs that meet exactly your requirements and aim to provide you with the good practices of surgery and peri operative care technics. Topics include: anesthesia, analgesia, asepsis, peri operative care, surgical procedures. Contact us: [email protected] Charles River and Professor René Rémie are combining their expertise to offer surgery training courses combining lectures with hands-on exercises to ensure that you receive the most comprehensive training experience. Please contact us to learn more about future sessions: [email protected] Customised Surgical Procedures Many of our specialised surgical offerings were developed based on customer demand. If you are interested in a surgically altered model that is not listed on the previous pages, please contact technical assistance to discuss the development of a customised procedure. Consult us: [email protected] On-site Surgery Charles River offers surgical procedures performed by our surgeons at your site. Quotations are established individually for each project depending on the complexity and the number of procedures to be performed. Consult us: [email protected] From Surgery to Protocol Surgically prepared animals are available as «ready-to-use models» for your research protocols. Charles River can also manage many aspects of your in vivo protocols, by: compound administration collecting blood for your pharmacokinetic studies collecting many body fluids such as CSF, urine, performing specific clinical observations and organ collection. Please contact technical assistance to discuss your project and see how Charles River could help you design and perform your protocols. 47

58 Biospecimens BIOSPECIMENS Tissues and Organs Charles River is able to supply normal tissues and organs from various species. The prices relate to the cost per biospecimen, not per donor animal. Surcharges will be added to cover special handling where individually sampled biospecimens, and custom collection protocols are required. Specimens are shipped in insulated dry ice igloos. RATS, MICE, GUINEA PIGS, RABBITS, HENS Adrenal Vessels - Bladder - Brain Cerebrospinal Fluid - Colon - Eyes - Jejunum - Heart - Ileum - Kidney - Liver - Lung - Milk (per ml) - Oesophagus - Pancreas - Pituitary - Prostate - Salivary Gland - Stomach - Skin (shaved) - Spinal Cord - Spleen - Tails - Testis Thymus - Thyroid - Urine (per ml) - Uterus. Please enquire for availability of other biospecimens Blood Products Blood, serum, and plasma can be collected from various species, including rodents and lagomorphs. Collection of Sera and Plasma Sera will be collected from coagulated blood. After centrifugation sera are placed in different sized tubes or vessels. The plasma and blood is collected in monovettes that include an anticoagulant. Standard anticoagulants are : Lithium-heparin (15 IU * heparin / ml blood) and sodium-heparin or Potassium-EDTA K3 or K2 (1.6 mg/ml blood) Other anticoagulants, as : Sodium citrate solution (0,5 ml citrate solution per 5 ml blood). Citrate solution: 3.13 % sodium citrate dihydrate = ml/l Alsever s solution 25/50% are also available upon request. Transport of Blood Products and Biospecimens Serum and plasma are stored at -20 C and usually transported on dry ice. Delivery charges and VAT are extra. Blood, serum, and plasma will be transported by our own delivery trucks, by mail, or a courier express service. Transportation charges are calculated according to the destination and the means of transport used. Packaging Price - Polystyren container (isotherm) 20,50 Insulated, cooled (+4 ) 24,30 Insulated, dry ice 80,00 Mice and Rats Description Amount in ml Outbred Mouse Inbred Mouse Outbred Rat Inbred Rat OF1, NMRI and C57BL/6 and OFA, Wistar Han Fischer Rats CD1 mice BALB/c mice and CD Rats Price - /tube Price - /tube Price - /tube Price - /tube Blood 1 7,05 28,55 4,05 7, ,35 Enquire 19,05 45, ,40 Enquire 37,35 88,15 Plasma 1 12,35 Enquire 6,40 16, ,80 Enquire 30,10 Enquire ,15 Enquire 58,90 Enquire Serum 1 12,35 Enquire 6,40 16, ,80 Enquire 30,10 Enquire ,15 Enquire 58,90 Enquire Prices apply for mentioned strains without indication of age or sex. For other strains, please contact your local office for further information and prices. Other volumes (ml) available on request. Gerbils, Hamsters, Guinea Pigs and Rabbits Description Amount Gerbils Hamsters Amount Guinea Pigs Amount Rabbits in ml Price - / ml Price - / ml in ml Price - /tube in ml Price - /tube Blood ,93 6,72 1 3,70 1 2, On request On request 5 16, , , ,70 Plasma ,94 8,31 1 5,85 1 4, ,35 7, , ,70 >1001 On request On request 10 52,55 20 On request Serum ,18 7,61 1 5,85 1 4, ,62 7, , ,70 >1001 On request On request 10 52,55 20 On request 48

59 Antibody Production Protocols ANTIBODY PRODUCTION PROTOCOLS With our dual experience in breeding and service provision, Charles River is a flexible and reactive partner for conducting your immunisation protocols, from research quantity supplies to industrial production on a wide range of species from SPF rodents to large animals. The immunisation and sampling schedule is adapted to customer specifications. In accordance with Charles River s policy, a scientific justification and an ethical review are required prior to conducting any protocols. Polyclonal Antibody Production Price - Immunisation according to our standard protocol (1 rabbit) 404,00 I. Complete Package One Price - Peptide synthesis (purity >80%, 5-10mg, up to 15 AA included) Support in selecting the peptide Conjugation to KLH, BSA or OVA (2 mg peptide, 20 mg KLH) 1 364,00 Two rabbits, standard protocol One pre-immune serum, two serum samples, final bleeding II. Complete Package Two Complete package one, plus: 3x ELISA antibody titre control 1 571,00 III.Complete package Three Complete package two, plus: Preparation of a HYDRA-antigen affinity column (1 ml matrix) Affinity isolation of antigen specific antibodies out of 50 ml serum or cell culture supernatant Sequential elution of up to 2 fractions of different affinity 2 259,00 Purification control of monospecific antibodies ELISA quality control Detailed documentation, chromatograms Monoclonal Antibody Production In vitro production of hybridomas Basic Package Price - Immunisation of three BALB/c mice, four injections within 3 months Serum titre control by ELISA tests Spleen cell preparation, fusion with mouse myeloma cell line, distribution of hybridoma cells onto 96 well plates, selection of hybridomas, ten plates in total 6 488,00 Detection of specific antibody in culture medium of 96 supernatants by ELISA with one antigen Delivery of 20 supernatants with the strongest immune reactivity Delivery of five vital or cryopreserved positive clones Standard Package Price - Immunisation of three BALB/c mice, four injections within three months Serum titre control by ELISA tests Spleen cell preparation, fusion with mouse myeloma cell line, distribution of hybridoma cells onto 96 well plates, selection of hybridomas, 20 plates in total Detection of specific antibody in culture medium of 96 supernatants by ELISA with one antigen ,00 Delivery of 30 supernatants with the strongest immune reactivity Delivery of ten vital or cryopreserved positive clones In vivo production Charles River requires a scientific justification and ethical review before accepting any protocol. Charles River France recently opened a new lab dedicated to cell culture. Our programme of monoclonal antibody production on mice (BALB/c J or N, Swiss nude, BALB/c nude) includes cell culture, pristanisation, hybridoma injection, ascites collection and IgG dosage. Additional antibody services are available including antigen synthesis as well as purification and labelling of antibodies. Contact your local office for detailed information about these offerings (see page 6). 49

60 Alzet Osmotic Pumps ALZET Osmotic Pumps ALZET OSMOTIC PUMPS Charles River is the exclusive distributor of ALZET Osmotic Pumps for France, Germany, Austria, Switzerland, Belgium, Netherlands, Spain, Portugal, Italy, Hungary, Czech Republic, UK and Ireland. ALZET Osmotic Pumps are miniature infusion systems that deliver test agents at controlled rates into mice, rats, and other laboratory animals. In addition to systemic administration, targeted delivery to an area remote from the site of implantation can be achieved by attaching a catheter to the pumps. ALZET Osmotic Pumps offer a good alternative to repeated animal dosing by injection or oral gavage. Their continuous delivery eliminates peak and trough fluctuations and allows the effects of test agents to develop fully and reproducibly, particularly those with short half-lives. ALZET Osmotic Pumps help minimise animal stress that develops through frequent handling. They can eliminate the necessity for weekend and nighttime dosing. During infusion, no external connections are required, and the animals are untethered and unrestrained. Since ALZET Osmotic Pumps are fully implanted, they are tamperproof. Individual caging of the animals is not required. Comprehensive technical information is available online at Flow Moderator Test agent Semi permeable membrane Osmotic layer Impermeable reservoir Pump model Specifications Product Code 1 pack of 10 - * Volume Duration Release Rate 1003D 100 μl 3 days 1,0 μl/hr , D 100 μl 1 week 0,5 μl/hr , μl 2 weeks 0,25 μl/hr , μl 4 weeks 0,11 μl/hr , D 200 μl 1 day 8,0 μl/hr , μl 1 week 1,0 μl/hr , μl 2 weeks 0,5 μl/hr , μl 4 weeks 0,25 μl/hr , μl 6 weeks 0,15 μl/hr ,66 2ML1 2 ml 1 week 10,0 μl/hr ,70 2ML2 2 ml 2 weeks 5,0 μl/hr ,92 2ML4 2 ml 4 weeks 2,5 μl/hr ,74 * Each pack contains 10 mini-osmotic pumps, 10 flow moderators, 1 disposable filling tube and 1 instruction/specification sheet. Accessories Product Code Price per pack of 10 - Filling tubes 100 μl pumps ,68 Filling tubes 200 μl pumps ,68 Filling tubes 2 ml pumps ,68 PEEK Tubing 100 μl pumps ,60 PEEK Tubing 200 μl pumps ,60 PEEK Tubing 2 ml pumps ,60 Flow Moderators 100 μl pumps ,76 Flow Moderators 200 μl pumps ,76 Flow Moderators 2 ml pumps ,76 Coloured Flow Moderators 100 μl pumps BLUE ,00 Coloured Flow Moderators 100 μl pumps TEAL ,00 Coloured Flow Moderators 200 μl pumps BLUE ,00 Coloured Flow Moderators 200 μl pumps TEAL ,00 Coloured Flow Moderators 2 ml pumps BLUE ,00 Coloured Flow Moderators 2 ml pumps TEAL ,00 ALZAID compatibility kit ,04 Brain Infusion Kits Product Code Price per pack of 10 - BIK ,11 BIK ,11 BIK ,11 Cyanoacrylate adhesive (loctite 454), pack of 5 x 3 g tubes Enquire Cannula Holder ,00 Cannula Holder ,00 ALZET Pumps are sold in units of 10 pumps, together with one filling tube. The ALZAID Test Kit contains enough material to test up to 4 substances. Brain Infusion Kit units contain material for 10 infusions: 10 infusion cannulas, 10 vinyl catheter tubes, 40 spacers, 1 instruction leaflet. 50

61 Alzet Osmotic Pumps Catheters Price per 10 - Medical grade polyethylene (PE) and vinyl tubing - Sterile PE mm ID 15 cm length ,70 Vinyl mm ID 15 cm length ,84 Unsterile per metre - connects to all ALZET flow moderators PE mm ID / PE mm ID Enquire Special Catheters Product Code Price each - Rat Jugular Catheter ,69 Rat Femoral Catheter ,85 Rat Femoral Tapered Catheter - Custom order Enquire Rat Intrathecal Catheter ,17 Rat Intrathecal Catheter - Short ,17 Rat Intraperiteonal (IP) Catheter ,30 Mouse Jugular Catheter ,87 Mouse Jugular Catheter AL ,52 Mouse Jugular Catheter LT ,52 Mouse Intrathecal Catheter ,99 Mouse Intraperiteonal (IP) Catheter ,30 AutoClip Wound Closure System (9 mm) Price - AutoClip 100 clips ,77 AutoClip Kit 100 (includes Applier, Remover and 100 clips) ,05 AutoClip Kit 500 (includes Applier, Remover and 500 clips) ,22 AutoClip Applier ,45 AutoClip Remover ,33 NEW Reflex Wound Closure System (7 mm) Price - Reflex 100 clips ,80 Reflex Kit 100 (includes Applier, Remover and 100 clips) ,83 Reflex Kit 500 (includes Applier, Remover and 500 clips) ,70 Reflex Applier ,45 Reflex Remover ,96 Choose the best pump model for your study design Presently, there are 12 pump models available that differ in volume (100 μl - 2 ml), duration (1 day - 6 weeks) and delivery rate (0,11μl/h - 10 μl/h). Dosage variability can be achieved by modifying agent concentration; duration can be extended by serial implantation of the pumps. Bypass the Blood-Brain-Barrier For direct delivery to the cerebral ventricles and brain tissue, the pumps can be combined with the Brain Infusion Kit 1, 2 or 3. Animal Considerations Choose the right pump model to suit your animal and route of delivery. Model Code Mice Mice Rats Rats Subcutaneous Intraperitoneal Subcutaneous Intraperitoneal 1003D 1007D D g 20 g 20 g N/A 10 g 20 g 20 g 150 g ML1 2ML2 N/A N/A 150 g 300 g 2ML4 51

62 Associated Services Overview PHARMACEUTICAL QUALITY CONTROL (BIOLOGICAL TESTS) Charles River offers a set of tests conducted in compliance with Good Manufacturing Practices in our Pharmaceutical Facility (authorised by the French Health Authorities in 2004). Furthermore, the Pyrogen test activity is also cgmp compliant and registered with the Food and Drug Administration (FDA) since Sample preparation All types of preparation can be performed (raw materials and drug products or medical devices): weighing, dilution, cold or hot extraction, autoclaving Price - Sample preparation Custom protocol Upon request In vivo Pyrogen testing Tests are performed in a protected area including two housing rooms, one sample preparation room and one testing room. This is equipped with a fully integrated test management system, from temperature recording to interpretation of the results, in compliance with the European, US and Japanese Pharmacopoeias (other Pharmacopoeias on request). Tests are performed using rabbits that are bred in SPF units on the same site. Price - In vivo Pyrogen test Pre-test and test on 3 rabbits Upon request Abnormal toxicity test, Systemic injection test, Safety tests Our test unit includes housing rooms and a laboratory. Tests are performed in compliance with the European, US and Japanese Pharmacopoeais (other Pharmacopoeais on request) using SPF mice and guinea pigs sourced from Charles River barrier rooms. Abnormal toxicity test, Systemic injection test, Safety tests Price - Mouse Custom protocol Upon request Mouse + Guinea pig Custom protocol Upon request Biological Activity testing Tests are conducted in our Immunology and Cell Culture Laboratories. Testing methods include: ELISA, electro-immunodiffusion, and cellbased assays. For other methods, please contact us at [email protected] Price - Biological activity testing Custom protocol Upon request Cell culture and banking Custom protocol Upon request Other biological testing All biological tests (e.g., biological reactivity test USP88, irritation and skin sensitivity assays ISO , haemolysis test ) described in any Pharmacopoeia or Sponsor references can be performed. Species used are: rabbit, rat, mouse and guinea pig. Please contact [email protected] for further information. Price - Biological testing Custom protocol Upon request 52

63 Associated Services Overview OTHER QUALITY CONTROL TESTING Endotoxin and Microbial Detection: Endosafe and Accugenix The Endotoxin and Microbial Detection division provides a comprehensive portfolio of QC testing solutions. A full line of rapid LAL testing systems, including the Endosafe-PTS (portable handheld) and MCS (multi-cartridge), facilitate reliable and accurate endotoxin testing with FDA-licensed LAL cartridges, providing quantitative test results in about 15 minutes. PTS -based microbiological testing products are also available for glucan contamination and Gram determination. Our endotoxin testing solutions are complemented by the services of Accugenix, an FDA-registered, cgmp-compliant contract microbial testing service laboratory. Accugenix specializes in bacterial and fungal identification and strain typing of environmental isolates to meet internal quality standards and government regulations. Bolstered by broad-based, accessible technical support, our progressive technologies and proprietary methods of endotoxin and microbial testing ensure the safe manufacturing and timely release of your product. For more information on those programs, contact us: [email protected] Mouse Embryo Assay (MEA) The mouse embryo assay (MEA) is currently the most widely used bioassay to test for toxicity and functionality of media and devices used in medically assisted procreation. Our group utilizes fresh one- and two-cells embryos produced from B6D2F1 mice to perform this service. The embryos are collected and incubated in the culture media (or device) to be tested for a predetermined amount of time. After exposure, the embryos are then cultured for approximately hours in a defined and tested culture medium and scored for embryos development until blastocysts. Charles River requires an 80% development rate from its control and test article/medium for the result to be considered a passing score. Exposure conditions to test media or material are defined in collaboration with the customer. Tests are conducted in the embryology laboratory based in the Charles River Genetically Engineered Models and Services facility. Mouse Embryo Assay (MEA) Price - MEA testing 25 embryos exposed to media or product and tested for blastocyst development Upon request GLP MEA testing 25 embryos exposed to media or product and tested for blastocyst development Upon request 53

64 54

65 Research Animal Diagnostic Services Research Animal Diagnostic Services We are committed to providing you with the highest quality scientifi c support through laboratory animal heath surveillance and disease diagnosis.

66 Research Animal Diagnostic Services Our goal is to identify and incorporate the most analytically sensitive and specifi c technologies available in order to provide the most accurate and reproducible results. We perform rigorous research and development prior to the introduction of any new assay or technology and we implement standard operating procedures to ensure that your samples yield the correct results. For details regarding our services and reagents, including testing platforms, technology and sample submission, please visit or contact Charles River at [email protected] Research Animal Diagnostic Services Diagnostic Laboratory Locations We have multiple diagnostic laboratories to provide a local, convenient option to you. We receive live animals and samples for diagnostic testing at all of our laboratories. North America (Massachusetts and California, US) Europe (France) Asia (Japan) The same techniques and technologies are implemented at all of our diagnostic sites worldwide, giving you confi dence that we will provide the consistent results that you have come to expect from Charles River. Complimentary Shipping Materials We provide our clients with International Air Transport Association (IATA)-compliant sample and animal shipping containers (sample shipping materials, shipping labels and containers, liveanimal shippers, etc.). To receive materials, simply contact us at Consultation and Education Since health concerns vary greatly with facility size and research type, our Professional and Technical staff members can provide one-on-one consultation and educational presentations on topics, including but not limited to: Routine and quarantine health surveillance programme design or refi nement, including FELASA recommendations Results interpretation Prevalent infectious agents, outbreak detection and management Technical training for users of serology reagents and ILIMS Research Animal Health Surveillance (pages 55-64) PRIA (PCR Rodent Infectious Agent) panels for mouse and rat Health monitoring, serology, microbiology and additional tests for : - Mouse - Rat - Gerbil - Rabbit - Hamster - Guinea Pig Ferret testing services Simian testing services Serology reagents (MFIA, ELISA and IFA) for in-house surveillance Cell Line and Research Biologics Screening (pages 65-66) PCR Panels to screen for: Rodent infectious agents Human infectious agents NEW! Cell Line Examination and Report (CLEAR) Panel to detect cell line contamination Environmental Monitoring (page 67) Microbial/bioburden testing for water, feed and bedding Surface testing Health Data Management Internet Laboratory Information Management System (ILIMS)

67 Research Animal Diagnostic Services RESEARCH ANIMAL HEALTH SURVEILLANCE MOUSE Mouse Health Monitoring Protocols Customized Health Monitoring protocols available upon request. Services offered as part of a Health Monitoring Protocol are also available individually. Protocol Price - Included tests Serology* PCR** Microbiology* Parasitology (1) Pathology*** HM Basic 230,00 - HM Basic M. pulmonis, C. bovis, 397,00 - (Immunodeficient Models) Pneumocystis sp Upper respiratory Endoparasite A gross necropsy HM Prevalent 237,00 Prevalent and gastro-intestinal and ectoparasite examination is HM Standard tract testing is examinations are included in 312,00 Tracking (FELASA quarterly compliant) included in included in all protocols HM Plus + Helicobacter all protocols all protocols 485,00 Assessment Plus Helicobacter sp**** (FELASA annually compliant) Sentinel Programme 2 nu/nu + 2 nu/+ SOPF sentinel mice. Shipping crates containing hydration, food and bedding. 755,00 HM Standard Crate delivery (Animal pickup service available on request). Sentinel Programme Pathology, Microbiology, Parasitology performed on 2 Nu/Nu. Tracking (for HM Standard) or Assessment Plus 1 032,00 HM Plus (for HM Plus) serology on 2 Nu/+. PCR for Helicobacter in HM Plus. * Agents included in these profiles are listed below under Mouse Serology and Mouse Microbiology. Additional agents (e.g., LDV) can be included for a fee. ** In addition to the included PCR tests, samples can be collected and screened for agent(s) of your choice (e.g., Helicobacter sp, Streptobacillus, M. pulmonis and Parvovirus) for an added fee. See page 56 for details. *** In the event of observation of a gross lesion, a sample is collected for histopathology. **** Helicobacter spp., H. hepaticus and H. bilis. Helicobacter tested by PCR for HM Plus, in compliance with FELASA annually. (1) Additional parasitology tests can be added for a fee: see page 61 for available tests. Mouse Serology Profiles Tracking Assessment Plus (compliant with (compliant with Agent (1) Parvovirus Prevalent FELASA quarterly) Assessment FELASA annual) MPV (1-5)** MVM Generic Parvovirus (NS-1) MHV** MNV TMEV (GDVII) EDIM (ROTA-A) SEND PVM REO MPUL LCMV MAV (1 & 2)** ECTRO K POLY MCMV HANT PHV (HANT) MTLV ECUN CARB Sample Suitability Control: Tissue Sample Suitability Control: Anti-Mouse IgG System Suitability Control: Mouse IgG Price * - 64,00 75,00 83,00 114,00 163,00 Serology Kits for submission of samples to the lab are available, please enquire for details. * Price per serum sample when submitted directly to the Serology Laboratory. Individual agent : 33,00. ** Multiple assays are included. MPV: several recombinant viral coat proteins (VP2) to detect seroconversion to MPV-1 through -5. MHV: a recombinant MHV nucleocapsid (N) protein and two highly purified whole-viral lysate antigens. MAV: highly purified whole-viral lysate antigens to both FL and K87. Boxes in red are agents in addition to FELASA recommendations. (1) Agent abbrevations are defined in the glossary of terms page 73. Mouse Microbiology** Upper Respiratory Culture Gastrointestinal Tract Culture Bordetella bronchiseptica Pasteurella multocida Staphylococcus aureus Citrobacter rodentium Pseudomonas aeruginosa Corynebacterium kutscheri Pasteurella pneumotropica (Jawetz and Heyl biotypes) Streptococcus (Beta-haemolytic) Klebsiella oxytoca Salmonella spp. Klebsiella oxytoca Pseudomonas aeruginosa Streptococcus pneumoniae Klebsiella pneumoniae Other bacteria Klebsiella pneumoniae Proteus spp. Other bacteria Proteus spp. Price* - 72,00 Price* - 52,00 * Panel price per sample when submitted directly to the Microbiology Laboratory; Additional charge applied with the submission of a whole animal. Individual assays are available upon request. Please contact us for sample specifications. ** Agents tested in all HM protocols, compliant with FELASA guidelines. Streptobacillus moniliformis and Clostridium piliforme included in all profiles by gross necropsy observation. 55

68 Research Animal Diagnostic Services PRIA Panels for Mouse Health Surveillance/Quarantine Sample pooling: For no additional fee, you can combine up to 10 samples (e.g. one fecal pellet each from 10 animals) and submit as one pool for PCR testing. Many sample types can be pooled depending on the testing process and the agent of interest. Please contact Charles River regarding pooling of samples for PCR testing. Custom panels: Available upon request. Individual Agent Testing: All agents listed in the table below can be tested for individually ( 87,00 per agent). Mouse Mouse Mouse Mouse Mouse Sample Enteric Prevalent Surveillance FELASA* Surveillance Agent Type PRIA PRIA PRIA PRIA Plus PRIA Fur mites** (Myobia, Myocoptes, Radfordia) fur swab Pinworm** (Aspiculuris and Syphacia) feces and anal swab Parasites Cryptosporidium feces Giardia (G. lamblia and G. muris) feces Spironucleus muris feces Mouse hepatitis virus (MHV) feces Mouse parvoviruses** (MPV-1, MPV-2, MPV-3, MPV-4, MVM) feces Viruses Mouse rotavirus (MRV/EDIM) feces Murine norovirus (MNV) feces Theiler's murine encephalomelitis virus (TMEV [GDVII]) feces Mouse adenovirus (MAV-1 & MAV-2) feces Cilia-associated respiratory bacillus oral swab Mycoplasma pulmonis oral swab Pneumocystis spp. lung Corynebacterium bovis feces Helicobacter sp** (Genus, H. hepaticus, H. bilis, H. typhlonius, H. rodentium, H. trogontum, feces H. ganmani) Pasteurella pneumotropica (Jawetz and Heyl biotypes) feces Citrobacter rodentium feces Corynebacterium kutscheri feces Salmonella spp. feces Bacteria / Fungi Streptobacillus moniliformis feces Controls Streptococcus (Beta-hemolytic; Group B) feces Staphylococcus aureus feces Clostridium pilforme feces Streptococcus (Beta-hemolytic; Group C) feces Streptococcus (Beta-hemolytic; Group G) feces Streptococcus pneumoniae feces Bordetella bronchiseptica feces Campylobacter spp. feces Klebsiella oxytoca feces Klebsiella pneumoniae feces Pseudomonas aeruginosa feces Staphylococcus xylosus feces Positive template Negative template Spike inhibition Nucleic acid recovery control (NARC) Price - 201,00 206,00 282,00 288,00 347,00 PRIA Kits for submission of samples to the lab are available, please enquire for details. *Panel is compatible with FELASA recommendations. Other tests (e.g. serology assays) can be added to provide a comprehensive screen (FELASA compliant). **Strain determination assays are performed on all positive results. 56

69 Research Animal Diagnostic Services RAT Rat Health Monitoring Protocols Customized health monitoring (HM) protocols available upon request. Services offered as part of a health monitoring protocol are also available individually. Protocol Price - Included tests* Serology* PCR** Microbiology* Parasitology (1) Pathology*** HM Basic 230,00 - HM Basic M.pulmonis, C.bovis, Upper Endoparasite 397,00 - (Immunodeficient Models) Pneumocystis sp respiratory and & ectoparasite Gross necropsy HM Prevalent 237,00 Prevalent gastrointestinal examinations is included HM Standard tract cultures are are included with all protocols 312,00 Tracking (compliant with FELASA quarterly testing) included with with all protocols HM Plus + Helicobacter all protocols 485,00 Assessment Plus Helicobacter sp**** (compliant with FELASA annual testing) Sentinel Programme 755,00 2 SOPF sentinel rats. Shipping crates containing hydration, food and bedding, HM Standard Crate delivery (Animal pickup service available on request). Sentinel Programme 1 032,00 HM Standard or HM Plus profile on 2 sentinels. HM Plus * Agents included in these profiles/panels are listed below under Rat Serology and Rat Microbiology. ** In addition, samples can be collected for PCR and screened for agent(s) of your choice (e.g., Helicobacter, Parvovirus, Pneumocystis sp.) for an added fee. See page 58 for details. *** In the event of observation of a gross lesion, a sample is collected for histopathology. **** Helicobacter spp., H. hepaticus and H. bilis. Helicobacter tested by PCR for HM Plus, in compliance with FELASA annually. (1) Additional parasitology tests can be added for a fee: see page 61 for available tests. Rat Serology Profiles Tracking Assessment Plus (compliant with (compliant with Agent (1) Parvovirus Prevalent FELASA quarterly) Assessment FELASA annual) RPV H-1 KRV RMV Generic Parvovirus (NS-1) SDAV RTV PCAR ("RRV") SEND PVM REO MPUL LCMV MAV HANT IDIR (ROTA-B) ECUN CARB Sample Suitability Control: Tissue Sample Suitability Control: Anti-Rat IgG System Suitability Control: Rat IgG Price* - 64,00 75,00 83,00 114,00 163,00 Serology Kits for submission of samples to the lab are available, please enquire for details. * Price per serum sample when submitted directly to the Serology Laboratory. Individual agent : 33,00. Boxes in red are agents additionally tested to FELASA recommendations. (1) Agent abbrevations are defined in the glossary of terms page 73. Rat Microbiology** Upper Respiratory Culture Gastrointestinal Tract Culture Bordetella bronchiseptica Pasteurella multocida Streptococcus (Beta haemolytic) Klebsiella oxytoca Salmonella spp. Corynebacterium kutscheri Pasteurella pneumotropica (Jawetz and Heyl biotypes) Streptococcus pneumoniae Klebsiella pneumoniae Other bacteria Klebsiella oxytoca Pseudomonas aeruginosa Proteus spp. Pseudomonas aeruginosa Klebsiella pneumoniae Staphylococcus aureus Other bacteria Proteus spp. Price* - 72,00 Price* - 52,00 * Panel price per sample when submitted directly to the Microbiology Laboratory; an additional charge applied with the submission of a whole animal. Individual assays are available upon request. Please contact us for sample specifications. ** Agents tested in all HM protocols, compliant with FELASA guidelines. Streptobacillus moniliformis and clostridium piliforme included in all profiles by gross necropsy observation. 57

70 Research Animal Diagnostic Services PRIA Panels for Rat Health Surveillance/Quarantine Sample pooling: For no additional fee, you can combine up to 10 samples (e.g. one fecal pellet each from 10 animals) and submit as one pool for PCR testing. Many sample types can be pooled depending on the testing process and the agent of interest. Please contact Charles River regarding pooling of samples for PCR testing. Custom panels: Available upon request. Individual Agent Testing: All agents listed in the table below can be tested for individually ( 87,00 per agent). Agent Rat Rat Rat Rat Rat Sample Enteric Prevalent Surveillance FELASA* Surveillance Type PRIA PRIA PRIA PRIA Plus PRIA Fur mites** (Myobia, Myocoptes, Radfordia) fur swab Pinworm** (Aspiculuris and Syphacia) feces and anal swab Parasites Viruses Giardia (G. lamblia and G. muris) feces Spironucleus muris feces Rat coronavirus (RCV, SDAV) feces Rat parvoviruses** (RPV, KRV, RMV, H-1) feces Rat theilovirus (Theiler's-like virus of rats [RTV]) feces Mouse adenovirus (MAV-1 & MAV-2) feces Cilia-associated respiratory bacillus oral swab Mycoplasma pulmonis oral swab Pneumocystis spp. lung Helicobacter sp** (Genus, H. hepaticus, H. bilis, H. typhlonius, H. rodentium, H. trogontum, feces H. ganmani) Pasteurella pneumotropica (Jawetz and Heyl biotypes) feces Corynebacterium kutscheri feces Salmonella spp. feces Streptobacillus moniliformis feces Streptococcus (Beta-hemolytic; Group B) feces Bacteria / Fungi Staphylococcus aureus feces Bordetella bronchiseptica feces Clostridium pilforme feces Streptococcus (Beta-hemolytic; Group C) feces Streptococcus (Beta-hemolytic; Group G) feces Streptococcus pneumoniae feces Controls Campylobacter spp. feces Klebsiella oxytoca feces Klebsiella pneumoniae feces Pseudomonas aeruginosa feces Staphylococcus xylosus feces Positive template Negative template Spike inhibition Nucleic acid recovery control (NARC) Price - 189,00 201,00 247,00 265,00 317,00 PRIA Kits for submisson of samples to the lab are available, please enquire for details. *Panel is compatible with FELASA recommendations. Other tests (e.g. serology assays) can be added to provide a comprehensive screen (FELASA compliant). **Strain determination assays are performed on all positive results. 58

71 Research Animal Diagnostic Services RABBIT/GERBIL Rabbit/Gerbil Health Monitoring Protocols Customized health monitoring (HM) protocols available upon request. Services offered as part of a health monitoring protocol are also available individually. Included tests Protocol Price - Serology* Microbiology* Parasitology Pathology** Upper respiratory Endoparasite and HM Basic 262,00 - Gross necropsy and gastrointestinal ectoparasite exams included with HM Plus tracts included included with 485,00 Assessment Plus all protocols (compliant with FELASA quarterly testing) with all protocols all protocols * Agents included in these profiles/panels are listed below under Gerbil Serology and Gerbil/Rabbit Microbiology. ** In the event of observation of a gross lesion, a sample is collected for histopathology. Rabbit Serology Profiles Agent (1) Assessment Plus ECUN CARB TREP CPIL RHDV PIV-1 PIV-2 REO ROTA LCMV TOXO Sample Suitability Control: Tissue Sample Suitability Control: Anti-Rabbit IgG System Suitability Control: Rabbit IgG Price * - 163,00 * Price per serum sample when submitted directly to the Serology Laboratory. Individual agent : 33,00. Boxes in red are agents additionally tested to FELASA recommendations. (1) Agent abbrevations are defined in the glossary of terms page 73. Gerbil Serology Profile Agent (1) LCMV Assessment Plus CPIL MHV REO SEND PVM MVM ROTA PIV-2 PIV-3 HANT PHV Sample Suitability Control: Tissue Price * - 163,00 * Price per serum sample when submitted directly to the Serology Laboratory. Individual agent : 33,00. Boxes in red are agents additionally tested to FELASA recommendations. (1) Agent abbrevations are defined in the glossary of terms page 73. Serology Kits for submission of samples to the lab are available, please enquire for details. Rabbit/Gerbil Microbiology Cultures** Upper Respiratory Culture Gastrointestinal Tract Culture Bordetella bronchiseptica Pseudomonas aeruginosa Klebsiella oxytoca Corynebacterium kutscheri (Gerbil only) Staphylococcus aureus Klebsiella pneumoniae Klebsiella oxytoca Streptococcus (Beta-haemolytic) Pseudomonas aeruginosa (Gerbil only) Klebsiella pneumoniae Streptococcus pneumoniae Salmonella spp. (Gerbil only) Pasteurella multocida Proteus spp. Proteus spp. Pasteurella pneumotropica Other bacteria Other bacteria Price* - 72,00 Price* - 52,00 * Panel price per sample when submitted directly to the Microbiology Laboratory; additional charge for submission of a whole animal. Individual assays are available upon request. Please contact us for sample specifications. ** Clostridium piliforme included in all protocols by gross necropsy, in compliance with FELASA recommendations. 59

72 Research Animal Diagnostic Services HAMSTER/GUINEA PIG Hamster/Guinea Pig Health Monitoring Protocols Customized health monitoring (HM) protocols available upon request. Services offered as part of a health monitoring protocol are also available individually. Protocol Price - Serology PCR Microbiology* Parasitology Pathology** Endoparasite and HM Basic 230,00 - Upper respiratory ectoparasite Lawsonia and gastrointestinal exams included Gross necropsy (Hamster only) tracts included in with all protocols included with HM Plus all protocols Dermatophytes all protocols (compliant with FELASA annual testing) 485,00 Assessment Plus Helicobacter sp included (Guinea Pig only) * Agents included in these profiles/panels are listed below under Hamster/Guinea Pig Serology and Hamster/Guinea Pig Microbiology. ** In the event of observation of a gross lesion, a sample is collected for histopathology. Hamster Serology Profiles* Agent (1) Assessment Plus (compliant with FELASA annual) SEND SV-5 PVM REO LCMV ECUN Sample Suitability Control: Tissue Sample Suitability Control: Anti-Hamster IgG System Suitability Control: Hamster IgG Price** - 163,00 * Applicable for Golden Syrian hamsters only. Other strains should be screened using the serology profile for miscellaneous rodent species. ** Price per serum sample when submitted directly to the Serology Laboratory Individual agent : 33,00. Boxes in red are agents additionally tested to FELASA recommendations. (1) Agent abbrevations are defined in the glossary of terms page 73. Guinea Pig Serology Profile Agent (1) SEND SV-5 PVM REO LCMV ECUN PIV-3 GAV MPUL GpCMV Assessment Plus (compliant with FELASA annual) Sample Suitability Control: Tissue Sample suitability Control: Anti-Guinea Pig IgG System Suitability Control: Guinea Pig IgG Price* - 163,00 * Price per serum sample when submitted directly to the Serology Laboratory. Individual agent : 33,00. Boxes in red are agents additionally tested to FELASA recommendations. (1) Agent abbrevations are defined in the glossary of terms page 73. Serology Kits for submission of samples to the lab are available, please enquire for details. Hamster/Guinea Pig Microbiology Cultures** Upper Respiratory Culture Gastrointestinal Tract Culture Bordetella bronchiseptica Pseudomonas aeruginosa Klebsiella oxytoca Corynebacterium kutscheri Staphylococcus aureus Klebsiella pneumoniae Klebsiella oxytoca Streptococcus pneumoniae Pseudomonas aeruginosa Klebsiella pneumoniae Streptococcus (beta-haemolitic) Salmonella spp. Pasteurella multocida Yersinia pseudotuberculoris Proteus spp. Pasteurella pneumotropica Proteus spp. Other bacteria (Jawetz and Heyl biotopes) Other bacteria Price* - 72,00 Price* - 64,00 * Panel price per sample when submitted directly to the Microbiology Laboratory; additional charge applied with submission of a whole animal. Individual assays are available upon request. Please contact us for sample specifications. ** Clostridium piliforme included in all profiles by gross necropsy observation in compliance with FELASA recommendations. Miscellaneous Rodent Species Serology Profile For applicable species (e.g., vole, Armenian hamster, cotton rat, ground squirrel), please contact us. Service Agents (1) Included Price - Assessment MHV, REO, SEND, PVM, MVM, LCMV, ROTA, PIV-2, PIV-3, HANT, PHV, ECUN 124,00 (1) Agent abbrevations are defined in the glossary of terms page

73 Research Animal Diagnostic Services Individual Rodent/Rabbit Health Surveillance PCR Assays The agents listed on pages 56 and 58 and in the table below can be tested for individually ( 87,00 per agent). Sample Pooling: For no additional fee, you can pool samples for PCR testing. Many sample types (e.g., feces) can be pooled depending on the testing process and the agent of interest. Please contact Charles River regarding pooling of samples for PCR testing. Encephalomyocarditis virus (ECMV) Guinea pig adenovirus (GAV) Guinea pig cytomegalovirus (GpCMV) Hantavirus hantaan (HANT) Hantavirus Seoul (SEO) K virus (K) Lactate dehydrogenase-elevating virus (LDV) Ljungen virus (LV) Lymphocytic choriomeningitis virus (LCMV) Mouse adenovirus (MAV-1 & MAV-2) Viruses Mouse cytomegalovirus (MCMV) Mouse thymic virus (MTLV) Mousepox (Ectromelia) (ECTRO) Pneumonia virus of mice (PVM) Polyoma virus (POLY) Rabbit picobirnavirus (RPBV) Rat cytomegalovirus (RCMV) Rat rotavirus (IDIR [ROTA-B]) Reovirus (Type 1 & 3) (REO) Sendai (SEND) Campylobacter coli Campylobacter jejuni Cryptosporidium Encephalitozoon cuniculi Other Lawsonia intracellularis NEW Pasteurella multocida NEW Rabbit Pinworm (Passalurus ambiguus) Spironucleus muris Toxoplasma gondii Some assays listed in this section can be used to screen multiple species (e.g. mouse, rat, rabbit). To determine the host species for each agent, please refer to the Glossary of Terms on page 73. Rodent Parasitology Sample Type Test Price - Faecal Concentration Centrifugation (FCC)* 90,00 Feces* and anal swab* Pinworm PCR (Aspiculuris and Syphacia) 87,00 Cryptosporidium PCR 87,00 Giardia PCR (G. lamblia, G. muris) 87,00 Spironucleus muris PCR 87,00 Fur swab* Furmite PCR (Myobia, Myocoptes, Radfordia). 87,00 Tape Tape Test for Ectoparasites 39,00 Live animal Tape Test for Endoparasites 39,00 Direct Exam for Ectoparasites 103,00 Direct Exam for Endoparasites 103,00 *Up to 8 samples for FCC and 10 for PCR can be pooled and tested as a single group with one result reported. Pathology We offer full-service diagnostic histopathology, either live animal submission or by direct submission of fixed tissues, paraffin blocks or slides. You can choose from routine and specialised necropsy procedures such as whole-body perfusion and collection of frozen tissues for RNA analysis. We offer histological evaluation of tissues from multiple species, complete tissue processing and slide preparation and/or routine and specialised staining techniques, as well as contract slide preparation and/or evaluation. Please enquire for pricing and further details. As part of the HM protocol, gross lesions are collected for histopathology. Pathology services Price - per animal Complete necropsy 104,00 Standard histology examination 76,00 Blood or faecal pellet sampling 24,00 Miscellaneous organ sampling (liver, kidney, spleen, lung, skin, mesenteric lymph nodes) Enquire Individual Agent Rodent / Rabbit serology Tests Price - Multiplexed Fluorometric ImmunoAssay (MFIA ) 33,00 Indirect Fluorescent Antibody (IFA) Test 33,00 Lactate dehydrogenase elevating virus (LDV)* 27,00 Rapid Plasma Reagin (RPR) test for Rabbit TREP 33,00 * Primary test for lactate dehydrogenase (LDH) enzyme, confirmation performed using LDV PCR assay. 61

74 Research Animal Diagnostic Services SIMIAN TESTING SERVICES Services available for samples only; Whole animals are not accepted. Service Item Included Price - Herpes B virus only HBV 44,00 Macaque Tracking SIV, SRV, STLV, HBV, MV 52,00 Serology* Macaque Assessment Macaque Tracking and SFV, CMV, MRV, SV-40, SVV 86,00 Baboon Tracking HVP-2, STLV, SIV, SA-11, MV 52,00 African Green Tracking SA-8, STLV, SIV, SA-11, MV 52,00 Blood Panel SRV, STLV, SIV, SFV, MRV-2/PRV-2, MAL, LCVO 253,00 Blood - Individual Agent** Pick One 102,00 Infectious Disease PCR Faecal Panel Campylobacter, Helicobacter, Salmonella, Shigella, Yersinia (Y. enterocolitica and Y. pseudotuberculosis) 217,00 Faecal - Individual Agent** Pick One 87,00 Serology* and Combination Screen - Infectious Disease PCR Individual Agent PCR and Serology for either SRV, SIV, or STLV 52,00 Simian Cultures Campylobacter, Salmonella, Shigella 102,00 SAL and SHIG Salmonella, Shigella 50,00 SAL Salmonella 46,00 Microbiology SHIG Shigella 46,00 CAMPY Campylobacter 46,00 YERS Yersinia 46,00 Other*** Other*** 46,00 Liver Profile See page 67 for details 43,00 Clinical Chemistry Lipid Profile See page 67 for details 38,00 Kidney Profile See page 67 for details 45,00 Complete Profile See page 67 for details 54,00 Parasitology Faecal Concentration Centrifugation (FCC) Ova and cysts of endoparasites 91,00 Histopathology Histopathology services Customized upon request Prices upon request *Service available for Old World simian species only. **Cost includes DNA extraction and the individual agent assay. ***Please contact Charles River for a full listing of microbiological agents. For a glossary of terms, see page 73. FERRET TESTING SERVICES Charles River offers the following services to screen your ferret colonies: Infectious disease PCR Clinical Chemistry Microbiology Parasitology Histopathology Please contact us at [email protected] for further details, agent list and pricing. 62

75 Research Animal Diagnostic Services Serology Reagents MFIA Reagents MFIA Bead Mixture* (Each unit contains 0.3ml and is sufficient for 1 plate of 96 tests.) Item Description Price - Mouse Parvovirus MPV-1, MPV-2, MPV-5, MVM, NS ,00 Mouse Prevalent Parvovirus Profile and MHV, MNV, TMEV (GDVll), EDIM (ROTA-A) 2 700,00 Mouse Tracking Prevalent Profile and SEND, PVM, REO, MPUL 4 501,00 Mouse Assessment Tracking Profile and LCMV, MAV, ECTRO, K, POLY 6 600,00 Mouse Assessment Plus Assessment Profile and MCMV, HANT, ECUN, CARB, CPIL, MTLV, PHV (HANT) 8 461,00 Rat Prevalent RPV, H-1, KRV, RMV, NS-1, SDAV, RTV, PCAR 2 791,00 Rat Tracking Prevalent Profile and SEND, PVM, REO, MPUL 4 141,00 Rat Assessment Plus Tracking Profile and LCMV, MAV, HANT, ECUN, CARB, CPIL, IDIR (ROTA-B) 7 164,00 Macaque Tracking SIV, SRV, STLV, HBV, MV 3 882,00 Macaque Assessment Tracking Profile and SFV, CMV, MRV, SV-40, SVV 6 210,00 Baboon Tracking HVP-2, STLV, SIV, SA-11, MV 3 882,00 African Green Tracking SA-8, STLV, SIV, SA-11, MV 3 882,00 Rabbit Assessment ECUN, CARB, CPIL, PIV-1, PIV-2, REO, ROTA, LCMV, TOXO 3 994,00 Guinea Pig Assessment SEND, SV-5, PVM, REO, LCMV, ECUN, PIV-3, MPUL 3 595,00 Hamster Assessment SEND, SV-5, PVM, REO, LCMV, ECUN 2 480,00 * Sample and System Suitability Controls are included in all profile mixtures. For a glossary of terms, see page 73. MFIA Control Sera Package (Each unit contains 0.25 ml [high/low range positive, non-immune] and is sufficient for 5 plates). Item Price - Mouse A for Parvovirus, Prevalent, Tracking 399,00 Mouse B for Assessment, Assessment Plus 1 306,00 Rat A for Prevalent, Tracking 397,00 Rat B for Assessment Plus 702,00 ** Customers must obtain a CITES permit to import these items. Item Not sold for use in commercial testing Price - Macaque Tracking 892,00 Macaque Assessment** 1 499,00 Baboon Tracking 892,00 African Green Tracking 892,00 Rabbit Assessment 698,00 Guinea Pig Assessment 364,00 Hamster Assessment 267,00 MFIA Supplemental Reagents (Each unit is sufficient for 5 plates.) Item Price - Primary Diluent (rodent and rabbit) 180,00 Primary Diluent (Simian) 180,00 Streptavidin-R-Phycoerythrin (SPE) 225,00 Conjugate for Mouse/Rat Samples 201,00 Conjugate for Simian Samples 504,00 Conjugate for Rabbit Samples 371,00 Conjugate for Guinea Pig Samples 189,00 Conjugate for Hamster Samples 557,00 Rodent / Rabbit ELISA* Reagents Item Species Unit Each Unit Price - Mouse Rat Guinea Pig Hamster Sufficient for: 96-well coated plates 1 plate 48 tests 213,00 Conjugate** 0.2 ml 10,000 tests 49,00 Control sera Positive (High or low score) 0.5 ml 10 plates 80,00 Control sera Negative 0.1 ml 10 plates 21,00 * See table above for available agents. ** Peroxidase-conjugated, affinity purified, goat antibody to species (IgG). Commercial use of Charles River serology reagents requires specific licensing. Commercial use is subject to royalties. Please enquire for further details. 63

76 Research Animal Diagnostic Services Rodent / Rabbit IFA* Reagents Item Species Unit Each Unit Price - Mouse Rat Guinea Pig Hamster Rabbit Gerbil Sufficient for: 18-well coated slides 1 slide 18 tests 107,00 Conjugate 0.1 ml 180 tests 49,00 Control sera Positive or Negative 0.1 ml 10 slides 21,00 * See table below for available agents. Platform Agent ELISA IFA CARB CPIL ECTRO ECUN EDIM GDVII H-1 HANT K KRV LCMV For a glossary of terms, see page 73. Platform Agent ELISA IFA MARTH MAV MCMV MHV MNV MPUL MPV MTLV MVM NS-1 PHV PCAR Platform Agent ELISA IFA PIV-3 POLY PVM REO RMV RPV RTV SDAV SEND SV-5 TOXO Simian IFA Reagents Item Each Unit Unit Sufficient for: Price - 18-well coated slide* 1 slide 18 tests 107,00 Conjugate** 0.1 ml 180 tests 42,00 Control sera** - Positive or Negative 0.1 ml 10 slides 25,00 *Available agents: SIV, STLV, HVP, SFV, SCMV, SVV, SV-40, MV, SRV-2, SRV-5, HEP-A. **Outside of the United States, customers must obtain a CITES permit to import control sera for the following agents: SFV, SCMV, SV-40, MV. Serology Kit Immunocomb Each Unit Unit Sufficient for: Price - (1) Murine ImmunoComb Kit I - Coronavirus (MHV, SDA), MPUL & SEND 1 kit 30 samples 459,00 Murine ImmunoComb Kit II - MHV, MVM, MPV-1/-2, MNV 1 kit 30 samples 459,00 (1) Prices are subject to exchange rate variation. 64

77 Research Animal Diagnostic Services CELL LINES AND RESEARCH BIOLOGICS SCREENING Our TaqMan PCR assays are employed so you can perform precautionary screening on your research biologics (e.g. primary and continuous cell lines, cell line products, ascities, purified antibodies) to confirm that they are free of infectious agents and maintain the validity of your in vivo research. In addition to the Rodent and Human PCR Panels (below and on page 66), custom panels and individual agent testing are available upon request; please enquire for pricing. Please note that this service is available for research purposes only. PCR Panels to Screen Cell lines and Research Biologics for Rodent Infectious Agents Mouse Rat Mouse/Rat Essential Essential Comprehensive Agent Type Panel Panel Panel Murine norovirus (MNV) RNA Mouse parvoviruses* (MPV-1, MPV-2, MPV-3, MPV-4, MVM) DNA Mouse hepatitis virus (MHV) RNA Reovirus (Type 1 & 3) (REO) RNA Lymphocytic choriomeningitis virus (LCMV) RNA Lactate dehydrogenase-elevating virus (LDV) RNA Mouse rotavirus (MRV/EDIM) RNA Theiler s murine encephalomyelitis virus (TMEV; [GDVII]) RNA Mousepox (Ectromelia) (ECTRO) DNA Hantavirus hantaan (HANT) RNA Hantavirus seoul (SEO) RNA Polyoma virus (POLY) DNA K virus (K) DNA Mouse adenovirus (MAV-1 & MAV-2) DNA Mouse cytomegalovirus (MCMV) DNA Mouse thymic virus (MTLV) DNA Pneumonia virus of mice (PVM) RNA Sendai (SEND) RNA Rat cytomegalovirus (RCMV) DNA Rat theilovirus (Theiler s-like virus of rats [RTV]) RNA Rat parvoviruses* (RPV, KRV, RMV, H-1) DNA Rat rotavirus (IDIR) RNA Rat coronavirus (RCV, SDAV) RNA Mycoplasma (genus) (including Acholeplasma laidlawii) DNA Mycoplasma pulmonis DNA Positive template control Control Negative template control Control Spike inhibition control Control Nucleic Acid Recovery Control (NARC) Control Price - 414,00 362,00 587,00 *Strain determination assays are performed on all positive results. For a glossary of terms, see page 73. NEW! Cell Line Examination and Report (CLEAR) Panel to Detect Cell Line Contamination We now offer CLEAR Panel that can detect less than 0.5% inter-species contamination using TaqMan PCR assays. Cells originating from mouse, rat, Chinese hamster, golden Syrian hamster, human and non-human primate (NHP) can be differentiated. CLEAR Panel can also be included with the rodent/human PCR panel or Mycoplasma testing at a low cost. Add to a Cell Line Panel Stand Alone Service or Mycoplasma PCR Species Detected at less than 0.5% contamination Price Price Mouse, Rat, Human, Non-human Primate, Chinese Hamster, Golden Hamster 74,00 43,00 65

78 Research Animal Diagnostic Services PCR Panels to Screen Cell lines and Research Biologics for Human Infectious Agents Human Human Human Agent HEP/HIV Panel Essential Comprehensive Polyomavirus (John Cunningham virus) Polyomavirus (BK virus) Herpesvirus type 6 Herpesvirus type 7 Herpesvirus type 8 Parvovirus B19 Epstein-Barr virus Hepatitis A virus Hepatitis B virus Hepatitis C virus Papillomavirus type 16 Papillomavirus type 18 Human T-lymphotropic virus Human cytomegalovirus Human immunodeficiency virus type 1 Human immunodeficiency virus type 2 Adeno-associated virus Human foamy virus Mycoplasma (genus) (including Acholeplasma) Lymphocytic choriomeningitis virus Hantavirus hantaan Hantavirus seoul Spike inhibition control Nucleic acid recovery control (NARC) Positive template control Negative template control Price - 174,00 436,00 502,00 NEW! Cell Line Examination and Report (CLEAR) Panel to Detect Cell Line Contamination We now offer CLEAR Panel that can detect less than 0.5% inter-species contamination using TaqMan PCR assays. Cells originating from mouse, rat, Chinese hamster, golden Syrian hamster, human and non-human primate (NHP) can be differentiated. CLEAR Panel can also be included with the rodent/human PCR panel or Mycoplasma testing at a low cost. Add to a Cell Line Panel Stand Alone Service or Mycoplasma PCR Species Detected at less than 0.5% contamination Price Price Mouse, Rat, Human, Non-human Primate, Chinese Hamster, Golden Hamster 74,00 43,00 In Vivo Biosafety Testing All tests can be performed to be GLP-compliant. Customised study design is available. For details, please contact us. Test Price - per Article GLP Test Mouse Antibody Production (MAP) (18 viruses) 2 252,00 MAP with LCMV Challenge 2 471,00 Rat Antibody Production (RAP) (12 viruses) 2 231,00 Hamster Antibody Production (HAP) (11 viruses) 2 209,00 General Safety Test 2 326,00 Detection of Inapparent Virus* Prices upon request Tumorigenicity Study** Prices upon request * This test can also be conducted to meet the requirements of the FDA Guidance for industry for viral Vaccines (February 2010). ** As outlined in the 1993 Points to consider in the Characterization of Cell Lines Used to Produce Biologicals. 66

79 Research Animal Diagnostic Services Clinical Pathology Service Clinical Chemistry Profiles In addition to the profiles listed below, custom profiles and individual tests are available. Please inquire for pricing and additional assay list. Assay Abbreviation Lipid Liver Kidney Complete Alanine aminotransferase ALT Albumin ALB Alkaline phosphatase ALK Aspartate aminotransferase AST Bilirubin (total) TBIL Total protein TP Gamma-glutamyl transferase (simian only) GGT Blood urea nitrogen BUN Calcium CA Cholesterol CHOL Creatinine CREAT Glucose GLU Inorganic phosphate PHOS Triglycerides TRIG High-density lipoprotein HDL Low-density lipoprotein LDL Chloride CL Potassium K Sodium NA Sample suitability control CNTRL Price - 38,00 43,00 45,00 54,00 In addition to the profiles listed above, the following are available (prices upon request): Cardiovascular profile Thyroid profile Diabetes profile Custom profiles Anemia profile Individual tests Environmental Monitoring Microbial/Bioburden and Sterility Testing Test Type Microbial/Bioburden Sterility Price - Water 143,00 61,00 Rodent Feed 143,00 61,00 Bedding 143,00 61,00 Surface Testing Tests Price - Environmental Swab (culture) for rodent pathogens 143,00 Environmental Swab (PCR) for rodent pathogens Prices upon request* Surface Swab (culture) for relative count (Bioburden) 61,00 RODAC Plate Count 15,00 per plate RODAC Plate Count with Gram stain 20,00 per plate *PCR testing for the agent(s) of your choice. Price may vary with agent selection. Please contact Technical Services for details. 67

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81 Genetically Engineered Models and Services For nearly 25 years, Charles River has delivered genetically engineered models and related services to biopharmaceutical companies, world renowned academic institutions and a host of government agencies globally. Today, GEMS (Genetically Engineered Models & Services) prides itself on being a onestop shop provider of integrated services, including customised breeding programmes, quarantine space, genetic testing, rederivation, cryopreservation, IVF and proof of concept studies. Genetically Engineered Models and Services

82 Genetically Engineered Models and Services Introducing ICM Charles River is pleased to announce the launch of our Internet Colony Management (ICM ) system. ICM is a revolutionary, custom designed software solution for both project and vivarium management. Capturing thousands of data points using tablet computers and RFID, ICM prioritises tasks and drives day-to-day activities. The data collected in the vivarium is instantly made available to project managers and clients through an online portal, where clients also have the option of initiating animal-related tasks at any time. ICM Features Improved data integrity through simple, sourcecaptured data inputs Real-time data sharing among animal care and project management staff and customers Two-way, data-rich customer portal to share information and direct animal / colony requests Extensive fi ltering and sorting capabilities to quickly navigate to the data you need Data export to Microsoft Excel to allow for custom data manipulation 360 data fl ow to ensure accuracy, confi rm task completion and manage colony goals In addition to its broad colony management features, ICM also serves as a repository of project information, such as current and past goals, extensive details on each colony, health reports, shipment history and a complete record of any tasks you have requested. With ICM, all of your animal and project information is just a mouse click away. To learn more about ICM or to view a video of the system in action, visit Genetically Engineered Models and Services

83 Genetically Engineered Models and Services GENETICALLY ENGINEERED MODELS AND SERVICES Service Description Price - Quarantine PRIA Quarantine 18 cages isolator, following the GEMS PRIA Quarantine protocol Upon Request Quarantine 18 cages isolator, following GEMS standard protocol with complete health report Upon Request Breeding All colonies are assigned a dedicated project manager and clients are granted access to Charles River's innovative Internet Colony Management (ICM) system. ICM provides a two-way communication portal with real-time data access, a comprehensive suite of colony management tools, and a complete historical record of all colonies housed at Charles River. Basic Isolator Reserved for homozygous breeding or boarding Upon request Genetic Isolator Heterozygous breeding, backcrossing, etc. Upon request Mouse Rapid Expansion I rederived animals delivered, with complete health report* 166 /animal produced Mouse Rapid Expansion II rederived animals delivered, with complete health report* 149 /animal produced Mouse Rapid Expansion III 121+ rederived animals delivered, with complete health report* 138 /animal produced Long-Term Rodent Ageing Holding animals to reach a specified age Upon request Comprehensive Colony Start-up Background characterisation of three animals, sperm cryopreservation, rederivation to produce 25 animals and PCR genotyping ,00 Mouse Rescue Package I Recovery of a line that is no longer producing offspring using in vitro fertilisation 6 064,00 Mouse Rescue Package II * Applicable for most strains. Recovery of a line that is no longer producing offspring using in vitro fertilisation and sperm cryopreservation 7 167,00 Rederivation Mouse Embryo Rederivation I (Rapid Rederivation) Mouse Embryo Rederivation II At least two visibly pregnant embryo recipient females delivered At least 10 rederived offspring delivered with complete health report, conventional colony held until project completion* 3 220, ,00 Mouse Embryo Rederivation III Expansion of a homozygous colony from 10 pairs, at least 10 rederived offspring delivered with complete health report, conventional colony 6 444,00 held until project completion* Mouse Embryo Reconstitution Mouse Sperm Rederivation I Mouse Sperm Rederivation II Mouse Sperm Reconstitution Rat Embryo Rederivation I At least 10 rederived offspring delivered if recovered from Charles River stock, with complete health report At least two visibly pregnant embryo recipient females delivered, includes sperm cryopreservation* At least 10 rederived offspring delivered with complete health report, includes sperm cryopreservation* At least 10 rederived offspring delivered if recovered from Charles River stock, with complete health report* At least 10 rederived offspring delivered with complete health report, conventional colony held until project completion 1 949, , , , ,00 Rat Embryo Rederivation II Expansion of a homozygous colony from a minimum 10 pairs, at least 10 rederived offspring delivered with complete health report, 9 217,00 conventional colony held until project completion* Rat Embryo Reconstitution * Applicable for most strains. At least 10 offsprings delivered if recovered from Charles River stock, with complete health report 3 314,00 69

84 Genetic Testing Services Service Description Price - Cryopreservation I CRYO Mouse Cryopreservation I Do-it-yourself sperm cryopreservation kit - includes instructions, materials, and media for cryopreserving 5 lines and media for IVF QC for 5 lines Cryopreservation of 300 embryos, most projects using wild type mice from Charles River* 3 570, ,00 Mouse Cryopreservation II Expansion of a homozygous colony and cryopreservation of 150 embryos * 3 534,00 Mouse Cryopreservation in vivo test Mouse Sperm Cryopreservation Mouse Sperm Cryopreservation in vivo test Rat Cryopreservation I Reimplantation of straw of quality control embryos in a pseudo-pregnant female up to birth Cryopreservation of sperm from two males, includes pre- and post-thaw QC, ~15 straws preserved Production of embryos from frozen sperm, reimplantation in a pseudo-pregnant female up to birth Cryopreservation of 300 embryos, projects using wild type rats from Charles River * 321, ,00 536, ,00 Rat Cryopreservation II Expansion of a homozygous colony and cryopreservation of 150 embryos * 5 300,00 Cryopreservation Storage Secure storage in two independent facilities 401,00 /year * Applicable for most strains. Model creation services C57BL/6NCrl - Small BlastoKit 10 straws of 40 C57BL/6NCrl morulae 3 267,00 C57BL/6NCrl - Large BlastoKit 40 straws of 40 C57BL/6NCrl morulae ,00 BALB/c-AnNCrl - Small BlastoKit 10 straws of 40 BALB/c-AnNCrl morulae 4 444,00 BALB/c-AnNCrl - Large BlastoKit 40 straws of 40 BALB/c-AnNCrl morulae ,00 ES Cell Injection Package I ES Cell Injection Package II ES cells injected into ~80 blastocysts, chimeric offspring returned with complete health report ES cells injected into ~80 blastocysts, chimeric offspring bred with wild type animals to confirm germline transmission, positive F1 offspring returned with complete health report Upon request Upon request Genetic Testing PCR Genotyping testing Upon request PCR set up Custom assay development or validation Upon request Q-PCR Transgenic zygosity testing Upon request Q-PCR Development Custom assay development or validation Upon request SNP Testing Single nucleotide polymorphism panel 155,00 SNP Development Custom assay development or validation 420,00 Expression Testing Tissue expression level testing 86,70 Expression Assay Development Custom assay development or validation 715,00 Relative Copy Number Analysis Transgenic copy number testing 46,90 Copy Number Development Custom assay development or validation 715,00 Background Strain Characterisation Analysis of genetic background 265,00 MAX-BAX Speed Congenics Fast development of congenic strains Upon request NOD Testing 28,55 SCID, Foxn 1 Testing 28,55 SNP QC Testing 28,55 Disease Model Testing 28,55 MHC Class I and II Testing 28,55 70

85 Insourcing Solutions SM Whether you outsource your research or conduct studies in-house, you may need consultative, training, staffi ng or additional space to administer an effi cient, cost-effective and successful programme. Charles River Insourcing Solutions SM offers it all. Our service contracts are customised to meet the unique needs of each research institution we support. Insourcing Solutions SM

86 Insourcing Solutions SM Service Page Staffi ng and Facility Management 71 Consulting 71 Training 71 Modular Buildings - A Turnkey solution 72 Insourcing Solutions SM

87 Insourcing Solutions SM Due to the dynamic nature of research, you may find your facility needing additional consulting, staffing and training resources to support your research programs. Charles River Insourcing Solutions SM meets this need with our integrated insourcing model. We work directly with you to implement the research support necessary to meet your program goals. A partnership with Insourcing Solutions SM can provide you with both long- and short-term functional support for your research programs. Staffing and Facility Management Depending on the research requirements, the staff you need may require qualifications ranging from a BA/BS to a PhD. We work with you to define the most appropriate combination of skills and qualifications to fulfill your facility s needs. We can provide a wide range of scientific talent, including, but not limited to: Managers (project, laboratory, animal facility, etc.) Veterinarians Veterinary Technologists Licensed Animal Technicians Cage to Benchtop Transgenic Technicians Aquatic Specialists Cagewash and Animal Husbandry Personnel Scientists Regulatory Specialists QA and QC Specialists Administrative Professionals Today, Insourcing Solutions SM has more than 800 employees staffing research facilities in the government, commercial and academic sectors, with over m² under management around the globe. Expert Consulting When establishing a new project or evaluating an existing one, our consulting services can assist you in a number of important ways, including: Facility Operations Animal Health Aquatics Regulatory compliance Animal care and use program and facility evaluations Facility engineering and design Biosecurity practices Development, implementation and evaluation of standard operating procedures (SOPs) With more than 65 years experience, backed by a professional team consisting of 600 PhDs, DVMs, and MDs, we offer both short- and long-term consultancy options to support your facility and research programs. Customized Training A highly trained staff is an integral component to achieving your research goals. Whether it is individual staff training in specific husbandry or the implementation of a complete continuing training program for your staff, Charles River can tailor a training program to suit your specific needs. Charles River team can help you in the design and implementation of an institutional training program that assures the competence of all staff involved in the care, breeding and use of animals for scientific procedures. We offer both didactic and hands-on instruction in actual and simulated research environments, as well as synchronous and asynchronous e-learning course design and deployment. Our expert trainers can design a program to fulfill your training requirements, while assuring regulatory compliance and upholding the scientific integrity of your research. Insourcing Solutions SM offers over 85 training courses in the following areas: Occupational health and safety Vivarium technical skills - Multi-species, tattoo, necropsy, surgery and anesthesia biomethodology - Cagewash, animal care and veterinary technician Professional Development - Leadership/Supervisory development - Animal welfare and enrichment - Training documentation and record keeping Regulatory compliance - Modular Professional Training (according to 2010/63/EC and FELASA recommendations) - GLP Train-the-trainer - Program development - Presentation skills - e-learning Our comprehensive training offerings also include a wide range soft skills courses and workshops that provide continuing education opportunities for animal research staff at all levels. 71

88 Insourcing Solutions SM MODULAR BUILDINGS - A TURNKEY SOLUTION Modules (Modular buildings) are prefabricated, customizable modular units that can be delivered to your site fully assembled, allowing for the rapid addition of workspace to your facility. Modular facilities meet and uphold stringent biocontainment and biosecurity requirements and allow for space to be added to your facility for a limited upfront investment and faster than conventional construction methods. The biological protection level of these units can be fully customized based on operational requirements. A Modular facility can be built to operate under negative or positive air pressure, depending on intended use (vaccine production, contaminated animal housing, or transgenic animal breeding vs. conventional and clean animal housing). From a temporary, short-term, small module to accommodate a special project to a permanent, 1000 m 2 complete animal facility, the modular building concept is the answer to your research space needs.based on space allocation and what it will be used for, our facility design and engineering team can customize a Module to meet your facility s specific needs. Building design flexibility Used alone or in connection with each other or an existing building Fully customizable interior design Easily transportable Flexible investment options Available for purchase or lease Alternative cost-effcient solution to traditional construction methods Customized solutions to meet your research needs Multispecies animal vivarium Laboratory facilities Containment and exclusion barriers, animal breeding and support space Commissioning and validation to GMP/GLP environments For more information about Insourcing Solutions SM, please contact us at [email protected] 72

89 Resources Resources Whether you ve run into an unfamiliar acronym, are wondering which animal models are available in your region or simply can t fi nd what you re looking for, this Glossary, Index and Stocks and Strains Worldwide appendix are here to help.

90 Resources Resources Page Glossary of Terms 73 Stocks and Strains Worldwide 74 General Terms and Conditions of Sale 78 Alphabetical Index 81

91 Glossary of Terms GLOSSARY OF TERMS Agent Abbreviation Family/Order Subfam/Genus Host Species* Aleutian disease virus ADV Parvoviridae Amdovirus F Chicken anemia virus CAV Circoviridae Gyrovirus C Cilia-associated respiratory bacillus CARB Unclassified Unclassified M, R, Rb Clostridium piliforme CPIL Clostridaceae Clostridium M, R, Rb, F Distemper virus CDV Paramyxoviridae Morbillivirus F Ectromelia virus (Mousepox) ECTRO Poxviridae Orthopoxvirus M Encephalitozoon cuniculi ECUN Pleistrophoridiae Encephalitozoon M, R, GP, H, Rb Encephalomyocarditis virus EMCV Picornaviridae Cardiovirus M, R Epizootic catarrhal enteritis ECE Coronaviridae Unclassified F Guinea pig adenovirus GAV Adenoviridae Mastadenovirus GP Guinea pig cytomegalovirus GpCMV Herpesviridae Betaherpesvirus GP Hantaan HANT Bunyaviridae Hantavirus M, R Influenza A virus INFA Orthomyxoviridae Influenzavirus A F Kilham rat virus KRV Parvoviridae Parvovirus R Lactate dehydrogenase-elevating virus LDH Arteriviridae Arterivirus M Ljungan virus LV Picornaviridae Parechovirus R Lymphocytic choriomeningitis virus LCMV Arenaviridae Arenavirus M, R, GP, H Minute virus of mice MVM Parvoviridae Parvovirus M Mouse adenovirus MAV Adenoviridae Mastadenovirus M, R Mouse cytomegalovirus MCMV Herpesviridae Betaherpesvirus M Mouse hepatitis virus MHV Coronaviridae Coronavirus M Mouse parvovirus MPV-1/-2/-3/-4/-5 Parvoviridae Parvovirus M Mouse pneumonitis virus K Papovaviridae Polyomavirus M Mouse rotavirus (Epizootic diarrhea of infant mice virus) MRV / EDIM / ROTA-A Reoviridae Rotavirus M Mouse thymic virus MTLV Herpesviridae Unclassified M Murine norovirus MNV Caliciviridae Norovirus M Mycoplasma arthritidis MARTH Mycoplasmataceae Mycoplasma M, R Mycoplasma pulmonis MPUL Mycoplasmataceae Mycoplasma M, R Parainfluenza virus (type 1) PIV-1 Paramyxoviridae Respirovirus Rb Parainfluenza virus (type 2) PIV-2 Paramyxoviridae Rubulavirus Rb Parainfluenza virus (type 3) PIV-3 Paramyxoviridae Respirovirus GP Parvovirus NS-1 NS-1 Parvoviridae Parvovirus M, R Pneumocystis carinii PCAR Pneumocystidaceae Pneumocystis R Pneumonia virus of mice PVM Paramyxoviridae Pneumovirus M, R, GP, H Polyoma virus POLY Papovaviridae Polyomavirus M Prospect Hill virus PHV Bunyaviridae Hantavirus M Rabbit adenovirus RbAV Adenoviridae Mastadenovirus Rb Rabbit rotavirus ROTA Reoviridae Rotavirus Rb Rat coronavirus/sialodacryoadentitis virus RCV, SDAV Coronaviridae Coronavirus R Rat cytomegalovirus RCMV Herpesviridae Betaherpesvirus R Rat minute virus RMV Parvoviridae Parvovirus R Rat parvovirus RPV Parvoviridae Parvovirus R Rat respiratory virus RRV See Pneumocystis carinii R Rat rotavirus (infectious diarrhea of infant rats) ROTA-B / IDIR Reoviridae Rotavirus R Rat theilovirus (Theiler s-like virus of rats) RTV Picornaviridae Theilovirus R Reovirus REO Reoviridae Orthoreovirus M, R, GP, H Rabbit picobirnavirus RPBV Picobirnaviridae Picobirnavirus Rb Sendai virus SEND Paramyxoviridae Respirovirus M, R, GP, H Seoul virus SEO Bunyaviridae Hantavirus M, R Simian virus 5 SV-5 Paramyxoviridae Rubulavirus GP, H Theiler s murine encephalomyelitis virus TMEV (GDVII) Picornaviridae Cardiovirus M, R Toolan s H-1 virus H-1 Parvoviridae Parvovirus R Toxoplasma gondii TOXO Sarcocystidae Toxoplasma Rb Treponema paraluis-cuniculi TREP Spirochaetales Treponema Rb *Species: M = mouse, R = rat, GP = guinea pig, H = hamster, Rb = rabbit, C = chicken, F = ferret Referenced only in Simian Testing Services Hepatitis A HEP-A Picornaviridae Hepatovirus Simian Herpes B virus HBV Herpesviridae Alphaherpesvirus Simian Herpes virus papio-2 HVP-2 Herpesviridae Alphaherpesvirus Simian Lymphocryptovirus - Old World LCVO Herpesviridae Lymphocryptovirus Simian (Old World) Macaque rhadinovirus-1 MRV Herpesviridae Rhadinovirus Simian Macaca and papio rhadinovirus-2 MRV-2/PRV-2 Herpesviridae Rhadinovirus Simian Malaria (Plasmodium) MAL Plasmodiidae Plasmodium Simian Measles virus MV Paramyxoviridae Morbillivirus Simian Simian agent 8 SA-8 Herpesviridae Simplexvirus Simian Simian cytomegalovirus SCMV / CMV Herpesviridae Cytomegalovirus Simian Simian foamy virus SFV Retroviridae Spumavirus Simian Simian immunodeficiency virus SIV Retroviridae Lentivirus Simian Simian rotavirus SA-11 Reoviridae Rotavirus Simian Simian T-lymphotropic virus STLV Retroviridae Deltaretrovirus Simian Simian type D retrovirus SRV Retroviridae Betaretrovirus Simian Simian varicella virus SVV Herpesviridae Varicellovirus Simian Simian virus 40 SV-40 Polyomaviridae Polyomavirus Simian 73

92 Strain Index Technical Literature Over the years, Charles River has been recognized as a reliable resource for publishing technical documentation that supports the interest of the research community. We have consistently dedicated the resources of our professional scientific staff toward researching issues that further the understanding of laboratory animal science. Publications may be found on our website at Outbred Mice Nomenclature Germany U.K France Italy Japan N America Crl:CD1(ICR) Crlj:CD1(ICR) Crl:CF1 Crl:CF1-Abcb1a mds Crl:CFW(SW) Crl:MF1(Hsd) Crl:NIHBL(S) Crl:NMRI(Han) Crl:OF1 Crl:SKH1-Hr hr Crl:SKH3(SKH2)-Hr hr Inbred Mice Nomenclature JAX Mice Strain Germany U.K France Italy Japan N America 129S2/SvPasCrl B6N-Tyr c /BrdCrCrl BALB/cAnNCrl BALB/cAnNCrlCrlj BALB/cByJ BALB/cJ C.BKa-Igh b /IcrCrl C3H/HeNCrl C3H/HeNCrlCrlj C3H/HeOuJ C57BL/6J C57BL/6NCrl C57BL/6NCrlCrlj CBA/CaCrl CBA/J DBA/1J DBA/1JNCrlj DBA/2J DBA/2NCrl DBA/2NCrlCrlj FVB/NCrl NC/NgaTndCrlj NOD/ShiLtJ SJL/J SJL/JOrlIcoCrl This strain is an authentic JAX Mice Strain derived from pedigreed mice from The Jackson Laboratory and bred by Charles River (CRL). Only The Jackson Laboratory and Charles River in Europe and Japan maintain colonies of JAX Mice strains which are derived from pedigreed mice from The Jackson Laboratory and are reinfused routinely with pedigreed mice to stabilize the genetic integrity and phenotypes of these strains. JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. 74

93 Strain Index Hybrid Mice Nomenclature JAX Mice Strain Germany U.K France Italy Japan N America B6C3F1/Crl B6C3F1/Crlj B6CBAF1/Crl B6CBAF1/J B6D2F1/Crl B6D2F1/Crlj B6D2F1/J CBAB6F1/Crl CB6F1/Crl CD2F1/Crl CD2F1/Crlj NMRCF1/Crl Immunodeficient Mice Nomenclature JAX Mice Strain Germany U.K France Italy Japan N America CAnN.Cg-Foxn1 nu /Crl CAnN.Cg-Foxn1 nu /CrlCrlj CB17.Cg-Prkdc scid Hr hr /IcrCrl CB17.Cg-Prkdc scid Lyst bg-j /Crl CB17/Icr-Prkdc scid /IcrIcoCrl CB17/Icr-Prkdc scid /IcrIcoCrlCrlj CBy.Cg-Foxn1 nu /J Crl:CD1-Foxn1 nu Crl:NIH-Lyst bg-j Foxn1 nu Btk xid Crl:NMRI-Foxn1 nu Crl:NU(Ico)-Foxn1 nu Crl:NU(Ncr)-Foxn1 nu Crl:NU-Foxn1 nu Crl:SHO-Prkdc scid Hr hr Crlj:CD1-Foxn1 nu NOD.CB17-Prkdc scid /IcrCrl NOD.CB17-Prkdc scid /J NOD.Cg-Prkdc scid Il2rg tm1wjl /SzJ Transgenic and Knockout Models Nomenclature JAX Mice Strain Germany U.K France Italy Japan N America B6.129P2-Apoe tm1unc /J B6.CBA-Tg(APOA1)427Bres/Crl C57BL/6Tg(TcraTcrb)1100Mjb/Crl C57BL/6Tg(TcraTcrb)425Cbn/Crl CBA;B10-Tg(H2K b -tsa58)6kio/crl Crl:WI(UL)-Tp53 m1hubr Crl:WI(UL)-Abcg2 m1hubr JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. 75

94 Strain Index Congenic Mice Nomenclature JAX Mice Strain Germany U.K France Italy Japan N America B6.SJL-Ptprc a Pecp b /BoyCrl B6.V-Lep ob /J BKS.Cg-Dock7 m +/+ Lepr db /J C57BL/6NCrl-Lepr db-lb /Crl Outbred Rats Nomenclature Germany U.K France Italy Japan N America Crl:CD(SD) Crl:CD-Prss8 hr Crl:LE Crl:LIS Crl:OFA(SD) Crl:OP(CD) Crl:OR(CD) Crl:SD Crl:WI Crlj:WI Crl:WI(Han) Crl:WI(WU) Crl:ZUC-Lepr fa Crlj:ZUC-Lepr fa Crl:ZUC(Orl)-Lepr fa Inbred Rats Nomenclature Germany U.K France Italy Japan N America BDIX/CrCrl BN/Crl BN/CrlCrlj BUF/CrCrl COP/CrCrl F344/DuCrl F344/DuCrlCrlj F344/IcoCrl F344/NCrl GK/TohiCskCrljCrl LEW/Crl LEW/CrlCrlj NBL/CrCrl PCK/CrjCrl-Pkhd1 pck /Crl SHHF/MccGmiCrl-Lepr cp /Crl SHR/NCrl SHR/NCrlCrlj SHROB/KolGmiCrl-Lepr cp /Crl SHRSP/A3NCrl SS/JrHsdMcwiCrl WAG/RijCrl WF/CrCrl WF/IcoCrl WKY/NCrl WKY/NCrlCrlj ZDF-Lepr fa /Crl JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. 76

95 Strain Index Hybrid Rats Nomenclature Germany U.K France Italy Japan N America ZSF1-Lepr fa Lepr cp /Crl Immunodeficient Rats Nomenclature Germany U.K France Italy Japan N America Crl:NIH-Foxn1 rnu Gerbils Nomenclature Germany U.K France Italy Japan N America Crl:MON(Tum) Guinea Pigs Nomenclature Germany U.K France Italy Japan N America Crl:HA Crl:HA-Hr hr Hamsters Nomenclature Germany U.K France Italy Japan N America Crl:LVG(SYR) Rabbits Nomenclature Germany U.K France Italy Japan N America Crl:KBL(NZW) Aged Animals Nomenclature JAX Mice Strain Germany U.K France Italy Japan N America C57BL/6J (Mice) Crl:OFA(SD) (Rats) Crl:WI(Han) (Rats) Consomic Rats Nomenclature Germany U.K France Italy Japan N America SS-Chr13 BN /McwiCrl JAX is a trademark of The Jackson Laboratory registered in the United States. All rights reserved. 77

96 General Terms and Conditions of Sale Charles River Laboratories, Inc. ( Charles River ) shall provide the products ( Products ) and services ( Services ) described in the Charles River invoice, quotation, protocol or statement of work ( SOW ) and Customer shall purchase the Products and Services pursuant to the specifications contained in the SOW and in accordance with the following terms and conditions: 1. Provision of the Products and Conduct of the Research Services. Charles River will provide the Products and conduct the Services in accordance with the SOW, which may be amended from time to time upon the mutual agreement of Charles River and the Customer. Charles River will adhere to all government laws, rules and regulations applicable to the provision of the Products or the conduct of the Services at the respective place of their delivery ( Applicable Law ). If an amendment requires additional or different work on the part of Charles River, Charles River may agree to conduct such work and will be paid an amount mutually agreed to by the parties. Deviations from the SOW may be made in an emergency without the Customer s approval, provided that Charles River shall use commercially reasonable efforts to obtain the Customer s verbal approval, which shall be subsequently confirmed by the Customer in writing. The parties acknowledge that during the course of performing the Services in accordance with the SOW, additional costs may be incurred by Charles River as a result of procedural changes which do not amount to or require a change in the SOW, but which are deemed necessary by Charles River to successfully perform the Services, and which could not be foreseen at the time of the preparation of the SOW. If such procedural changes occur, Charles River shall advise the Customer prior to their implementation and solicit the Customer s agreement as to the necessity and additional cost thereof. Should Charles River be unable to contact the Customer in advance, the Customer agrees that in order to maintain the integrity of the Services, Charles River may proceed accordingly and be entitled to recover such additional costs from the Customer upon presentation of an explanation of such procedural changes and the necessity thereof. Any Products purchased from Charles River shall be used by Customer in a safe manner, and in accordance with all applicable governmental rules and regulations. Customer, including its employees, agrees that all animals purchased from Charles River, descendants of those animals derived by inbreeding or crossbreeding, including unmodified derivatives of those animals or their descendants ( Animals ) shall not be: (i) used for any purpose other than the internal research of the Customer, (ii) bred (for sale or otherwise) or provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to such Animals, unless Charles River provides Customer with prior written authorization for deviation from these terms and conditions or a license. Customers should not, without the prior consent of Charles River, return animals or shipping containers to Charles River. Acceptance of delivery of Products or Services shall be deemed agreement to these terms and conditions. No other document attempting to negate or otherwise modify the terms hereof, including any purchase order or request for proposal, shall be binding upon Charles River, and instead these terms and conditions, including any special terms and conditions set forth separately, shall exclusively govern the sale of Products and Services by Charles River. The purchase of any Products conveys to the Customer the non-transferable right to use the Product and the components of the Products only in research conducted by the Customer and specifically in accordance with the SOW provided with the Products. The Customer cannot sell or otherwise transfer to a third party the Products or its components for Commercial Purposes. Commercial Purposes means any activity for cash or other consideration, including but not limited to (1) use of the Products or its components or materials made using the Products or its components in manufacturing, or to provide a service, information or data, or for clinical, therapeutic, diagnostic or prophylactic purposes or (2) resale of the Products or its components or materials made using the product or its components, except by licensed distributors, whether or not resold for use in research. The foregoing limitations are required by Charles River given the nature of the products sold, and to the extent that Charles River owns or controls (with the right to sublicense) patent rights or other intellectual property rights applicable to the Products or its intended use, those rights are licensed to Customer on a non-exclusive basis only for the uses expressly permitted above for the Products purchased. If Customer fails to comply with the foregoing limitations, in addition to any other remedies available to Charles River, the warranty provided for Products will be automatically voided. 2. Test Article If required for the performance of the Services, Customer will provide Charles River with sufficient amounts of all compounds, materials, animals, substances, devices and protocols meeting relevant specifications, including health and genetic data, ( Test Articles ), with which to perform the Services, as well as such complete and accurate data as is necessary to apprise Charles River of the identity, strength, purity, stability and composition or other appropriate characteristics of each batch, proper storage and safe handling requirements of the Test Articles, including a Material Safety Data Sheet (MSDS) or equivalent documentation. In addition, Customer will provide Charles River certification that the methods of synthesis, fabrication, or derivation of the Test Article have been documented by the Customer. All costs associated with shipping the Test Articles to Charles River shall be the responsibility of Customer, and Charles River shall not be responsible for any loss, damage or destruction of the Test Articles while in transit. All Test Articles and Products used in connection with the Services shall remain the property of Customer. 3. Inspections 3.1 Upon reasonable advance notice and during regular business hours, Charles River will permit the Customer to visit the Charles River facilities, in compliance with Charles River s biosecurity measures, where the Services is taking place to monitor Charles River s performance of the Services. 3.2 Charles River will notify the Customer as soon as practical in the event of any regulatory inspection of Charles River s facilities that directly impact the Services. In the event of an inspection of the Customer by a regulatory or administrative agency, Charles River will to the extent permissible under Applicable Law, consult with and allow the Customer to review and comment on any responses to such agency related to the inspection. 4. Reports 4.1 Charles River will keep complete and accurate records of the status and rogress of the Services if and as required by the SOW. Charles River will furnish a report or data containing information as specified in the SOW. All reports will be prepared in the standard format of Charles River. 4.2 Neither Charles River nor the Customer shall publish any report or data prepared for the Customer by Charles River without the prior written consent of the other, which shall not be unreasonably withheld. 4.3 In the event Charles River provides electronic access to the data, records, reports and other documentation and the Customer elects to use such electronic access, the use of such electronic access shall be governed by Charles River s standard access terms and conditions which are available on request. 5. Compensation 5.1 Prices will be as per the price list (if applicable, price of Products is based on highest weight range) on the day of delivery, and they do not include applicable Value Added Tax, packaging or shipment expenses. The price list may be adjusted by Charles River annually. The Customer will pay Charles River as set forth in the SOW. All invoices are due and payable thirty (30) days from the date of the invoice and the Customer agrees to pay all invoices submitted. All amounts not paid by the Customer when due may, at the option of Charles River, accrue interest from the applicable due date until paid, at a rate that is the higher of (i) the highest rate permitted under Applicable Law and (ii) 1.5 times the legal rate of interest in the applicable jurisdiction. In addition, Charles River may elect to cease or suspend work on the Services or withhold required reports or other deliverables if the Customer does not make payments when due and payable. 5.2 All applicable termination, delay or cancellation fees will be set forth in the SOW. 5.3 If in the judgment of Charles River, Customer s financial condition is precarious or there has been a materially adverse change in Customer s financial condition, Charles River shall have the right to demand payment or other assurances which it deems adequate before providing any additional Services. 6. Confidentiality 6.1 In the course of providing the Products or performing the Services, Charles River and Customer may exchange proprietary and confidential information. The parties will identify, in writing, such information as confidential and/or proprietary. If a party intends to disclose confidential information to the other party orally, the disclosing party shall (i) alert the other party of the confidential nature of the disclosure prior to the disclosure and (ii) provide written notice to the other party of the confidential nature and contents of such disclosure within ten (10) days of the original disclosure. Each party will use its commercially reasonable efforts to maintain such information in confidence and will employ reasonable and appropriate procedures to prevent its unauthorized publication or disclosure unless required by Applicable Law to disclose such information. Neither party shall use the other party s proprietary and/or confidential information for any purpose other than in performance of this Agreement. The obligations of confidentiality set forth in this Section 6 will survive termination or expiration of this Agreement for a period of five (5) years. The confidentiality provisions of this Section 6 shall not apply to any part of such information, which (i) is known to the receiving party at the time it was obtained from the disclosing party; (ii) is acquired by receiving party from a third party, and such third party did not obtain such information directly or indirectly from the disclosing party under obligation not to disclose; (iii) is or becomes published or otherwise in the public domain other than by violation of this Agreement by the receiving party; (iv) is independently developed by the receiving party without reference to or reliance upon the information provided by the disclosing party; or (v) is required to be disclosed by the receiving party to comply with applicable laws or governmental regulations; provided that the receiving party provides prompt written notice of such disclosure to the disclosing party and cooperates with the disclosing party s reasonable and lawful actions to avoid and/or minimize the extent of such disclosure. 7. Warranties 7.1 If applicable, the Customer warrants that it owns all rights, title and interest in the Test Articles furnished by the Customer to Charles River hereunder and the intellectual property related thereto, and that Charles River s use of any and all such Test Articles in connection with the Services does not infringe any third party rights. 7.2 Charles River warrants that to its knowledge the Products and Services shall conform to the specifications contained in the SOW and Applicable Law. Charles River does not warrant or represent that the results of the Services will be acceptable to any regulatory or governmental agency to which they are presented nor that the results of the Services will enable the Customer to further develop, market or otherwise exploit the Test Articles or any other product or service. SUBJECT TO MANDATORY WARRANTIES SET BY APPLICABLE LAW, THE WARRANTY BY CHARLES RIVER SET FORTH HEREIN IS IN LIEU OF ANY AND ALL OTHER REPRESENTATIONS OR WARRANTIES, EXPRESS, IMPLIED OR STATUTORY INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR FOR NON-INFRINGEMENT OF A PATENT, TRADEMARK OR OTHER INTELLECTUAL PROPERTY RIGHT. Any claim for breach of this warranty must be made in writing to Charles River within ten (10) business days after the Products are delivered or the completion of Services, after which time the Products or Services shall be deemed finally accepted. Risk of loss and title to the Products shall pass to Customer once the Products leave Charles River s facility or are delivered to a common carrier, as applicable. 8. Limitation of Liability 8.1 Charles River will not be liable for penalties or liquidated damages or for special, indirect, consequential, punitive, exemplary or incidental damages of any type or kind (including, without limitation, lost profits) regardless of whether any such losses or damages are characterised as arising from breach of contract, breach of warranty, tort, strict liability or otherwise, even if Charles River is advised of the possibility of such losses or damages, or if such losses or damages are foreseeable. 8.2 Charles River s liability, regardless of the form of action, shall be limited to actual damages and shall not exceed the total price paid for the Products or Services pursuant to which such liability arises. In no event shall Charles River be liable for any damages arising from or in connection with any decision by the Customer or any third party to further research, develop or market the Test Articles or any derivative or product or service related thereto (or to the Products or Services), or the use of the Test Articles or any product or derivative or service related thereto (or to the Products or Services). 78

97 General Terms and Conditions of Sale 8.3 Subject to the limitations set forth in this Section 8 and unless provided otherwise by Applicable Law, in the event that Charles River commits a breach of the warranty set forth in Section 7.2 above, Charles River s sole liability, and the Customer s sole remedy shall be for Charles River to replace the Products or issue a credit therefore, or conform the work or portion of the Services affected by the breach to the relevant specification. 9. Indemnities 9.1 Subject to the limitations of liability contained in Section 8 above, Charles River will defend, indemnify, save and hold harmless the Customer and its parent, subsidiaries and affiliates and their respective directors, officers, employees and agents from and against any claims, demands, suits, actions, causes of action, losses, damages, fines and liabilities, including reasonable professional fees ( Claims ) arising out of or in connection with or attributable to Charles River s gross negligence or wilful misconduct in provision of the Products or performance of the Services, and will pay any costs and damages which, by final judgement, after exhaustion of all reasonable appeals, may be assessed against them, provided that Charles River is given written notice of the Claims promptly after notice to the Customer and is given information, reasonable assistance, and sole authority to defend and/or settle the claim. 9.2 The Customer will defend, indemnify, save and hold harmless Charles River and its parent, subsidiaries and affiliates and their respective directors, officers, employees and agents from and against any Claims arising out of or in connection with or attributable to (a) the research, development, manufacture, distribution, use, sales or other disposition by the Customer, or any distributor, collaborator, customer, sublicense, representative or agent of the Customer, of the Test Articles and/or any other substances upon which the Services were performed or for which the Products were used, or (b) any infringement of any third party s patent rights or unauthorised use or misappropriation of its knowhow, or (c) the Customer s gross negligence or wilful misconduct, or (d) personal injury related to contact with the Products during visits to Charles River s facilities or after delivery of the Products to Customer, and will pay any costs and damages which, by final judgement, after exhaustion of all reasonable appeals, may be assessed against them, provided that the Customer is given written notice of the Claims within five (5) days of the date of notice to Charles River and is given information, reasonable assistance and sole authority to defend and/or settle the claim. 10. Ownership Any inventions and/or techniques for providing the Products or performing the Services which relate to the conduct of Charles River s business are and shall remain Charles River s exclusive property, including but not limited to; present and future documentation, scientific and technical data, test procedures and other information that is owned or licensed by Charles River and that is not developed hereunder. Charles River shall have the right to use concurrent control data as part of its general historical database. Any data, discoveries or inventions developed or generated which directly relate to any information or materials provided by the Customer hereunder, including without limitation new data, uses, processes or compositions directly relating to the information or materials provided hereunder shall be the exclusive property of the Customer. Charles River agrees to assist the Customer in securing for the Customer any patents, copyrights or other proprietary rights in such data, discoveries or inventions, and to perform all acts that may be reasonably required to vest in the Customer all right, title and interest in such data, discoveries or inventions, and Charles River shall be compensated at its standard rates for such assistance. All costs and expenses associated with establishing the Customer s rights therein shall be the Customer s responsibility. 11.Insurance Each party shall carry insurance sufficient to cover its interest or potential liabilities hereunder including, but not limited to worker s compensation, if applicable, and comprehensive general liability. 12.Force Majeure Except with respect to the payment of any amount due hereunder, neither party shall be considered in default of the performance of any obligation hereunder to the extent that the performance of such obligation is prevented or delayed by fire, flood, earthquake, explosion, strike, acts of terrorism, war, insurrection, embargo, government requirement, civil or military authority, animal activism, act of God, or any other event, occurrence or condition which is not caused, in whole or in part, by that party, and which is beyond the reasonable control of that party. 13.Termination 13.1 Unless otherwise specified in the SOW, the Customer shall have the right to terminate the SOW at any time without cause upon thirty (30) days prior written notice to Charles River. In the event of such termination, Charles River shall be paid for all Products provided or Services rendered through the effective date of termination, together with any additional expenses incurred in connection with the shutdown of the Services including without limitation any irrevocably committed costs and any cancellation or termination fee set forth in the SOW Either party may terminate this Agreement or SOW, as applicable, at any time upon thirty (30) days prior written notice to the other party, for material breach of the Agreement or SOW by the other party if such breach is not remedied to the non-breaching party s reasonable satisfaction within the thirty (30) day notice period Upon termination, neither party will have any further obligations, except that (i) the liabilities accrued through the date of termination and (ii) the obligations which by their terms survive termination, including the applicable confidentiality, record keeping, regulatory compliance, intellectual property and indemnification provisions of this Agreement, shall survive termination. 14. Dispute Resolution The parties shall attempt, in good faith, to resolve through negotiations any controversy, claim, or dispute arising out of this Agreement. In the event that negotiations are not successful, the controversy, claim, or dispute shall be submitted to third party mediation upon terms reasonably acceptable to the parties. If such claim, controversy or dispute is not resolved through mediation, upon written demand of either party, the claim, controversy or dispute shall be submitted to arbitration. Such arbitration shall take place in France, shall be conducted in English, and shall proceed in accordance with the United Nations Commission on International Trade Law Arbitration Rules (UNCITRAL) as at present in force. A record and transcript of the proceedings shall be maintained. Any award shall be made in writing and in reasonable detail, setting forth the findings of fact and conclusion of law supporting the award. The determination of a majority of the panel of arbitrators shall be the decision of the arbitrators, which shall be binding regardless of whether one of the parties fails or refuses to participate in the arbitration. All costs of such arbitration, except expert fees and attorneys fees, shall be shared equally by the parties. 15. Archiving 15.1 All reports and supporting documentation originating with Charles River are the Customer s property ( Materials ). Except as otherwise set forth in the SOW, and if applicable and requested in writing by the Customer, Charles River shall retain the Materials for a period of one year following the date of any final report, or for such shorter period as may be required by Applicable Law. At the end of such period, Charles River shall contact Customer to determine disposition of the Materials as follows: (a) extended storage of the Materials; (b) return of the Materials to Customer at Customer s expense or (c) disposal of Materials at Customer s expense. If the Customer requests Charles River to continue to store the Materials and Charles River agrees, the cost for storage of the Materials shall continue to be invoiced to the Customer at Charles River s then current rates. If the Customer fails to give such instructions, Charles River shall so notify the Customer, and if such instructions are still not forthcoming within thirty (30) days of said notification, then Charles River shall have the option of continuing storage of the Materials, which will be deemed to have been authorised for an additional period of not less than one (1) year or Charles River may return the Materials to the Customer at the Customer s expense. The Customer shall be liable for storage charges until the Materials are returned to the Customer. While the Materials are in transit to the Customer, all risk of loss or exposure to the Materials shall be borne by the Customer If the Materials require additional and/or special storage requirements, additional charges for storage shall be assessed and invoiced to the Customer. Invoices shall be issued annually in advance and are due and payable upon receipt and the Customer agrees to pay all invoices submitted Charles River s liability for archival services, regardless of the form of action, shall not exceed the fee paid for one year s storage of the Materials. In no event shall Charles River be liable for penalties or liquidated damages or for special, indirect, consequential punitive, exemplary or incidental damages of any type or kind (including, without limitation, lost profits) in connection with the storage of the Materials. Charles River shall have no liability for loss of specimens or information beyond its reasonable control, including losses caused by loss of refrigeration. 16. Miscellaneous 16.1 Notices. All notices from one party to the other will be in writing. Notices shall be sent by overnight courier, certified mail, return receipt requested, or by other means of delivery requiring a written acknowledged receipt. All notices shall be effective upon receipt Independent Contractor. The business relationship of the Charles River to the Customer is that of an independent contractor and not of a partner, joint venturer, employer, employee or any other kind of relationship Assignment. This Agreement, and the rights and obligations hereunder, may not be assigned or transferred by either party without the prior written consent of the other party, except that either party may assign this Agreement to an affiliated company or in connection with the merger, consolidation or sale of substantially all assets related to the Products or Services Entire Agreement. This Agreement sets forth the entire agreement and understanding between the parties, superseding any and all previous statements, negotiations, documents, agreements and understandings, whether oral or written, as to the subject matter of this Agreement (including and subsequent or conflicting terms and conditions of Customer). No modification or waiver of the provisions of this Agreement shall be valid or binding on either party unless in writing and signed by both parties Severability. In the event that any one or more of the provisions contained in this Agreement for any reason is held to be invalid, illegal or unenforceable in any respect, that invalidity, illegality or unenforceability will not affect any other provisions of this Agreement, and all other provisions will remain in full force and effect Applicable Law. This Agreement will in all events and for all purposes be governed by, and construed in accordance with, the laws of the jurisdiction from which the Products are provided or in which the Services are rendered (specifically excluding the United Nations Convention on the International Sale of Goods), without regard to any choice of law principle that would dictate the application of the law of another jurisdiction. Trademarks Charles River is a registered trademark of Charles River Laboratories, Inc. VAF and VAF/Plus are registered trademarks of Charles River Laboratories, Inc. Sprague Dawley is a registered trademark of Harlan Sprague Dawley, Inc., Indianapolis, IN. SD is a Harlan Sprague Dawley trademark. Fox Chase CB17 is a trademark of the Fox Chase Cancer Center. Fox Chase SCID is a registered trademark of the Fox Chase Cancer Center. Immortomouse is a registered trademark of the Ludwig Institute for Cancer Research. Polymerase Chain Reaction (PCR) analysis is performed pursuant to licensing arrangements with Roche Molecular Systems, Inc. and The Perkin-Elmer Corporation. Microsatellite analysis is performed pursuant to licensing arrangements with the Marshfield Clinic. Purina #5008 is a trademark of Nestle Purina Petcare Company. Research Diets is a trademark of BioDAQ genoway is a registered trademark of genoway S.A., Lyon, France Multiplexed Fluorometric ImmunoAssay (MFIA ) is a trademark of Charles River ImmunoComb is a registered trademark of Biogal-Galed Labs, Israel. TaqMan is a registered trademark of Roche Molecular Systems, Inc. BlastoKit is a trademark of Charles River I CRYO is a trademark of Charles River Charles River Laboratories, Inc.,

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99 Alphabetical Index RATS Common name Nomenclature Page Bcrp Knockout Crl:WI(UL)-Abcg2 tm1/hubr 17 BDIX BDIX/OrlCrl 19 BROWN NORWAY BN/Crl 15 BUFFALO BUF/CrCrl 19 CD Crl:CD(SD) 11 CD HAIRLESS Crl:CD-Prss8 hr 14 FISHER 344 F344/lcoCrl & F344/DuCrl 15 GK Rats GK/TohiCskCrljCrl 18 LEWIS LEW/Crl 15 LISTER HOODED Crl:LIS 11 LONG EVANS Crl:LE 12 NOBLE NBL/CrCrl 19 NUDE Crl:NIH-Foxn1 rnu 42 OFA Crl:OFA(SD) 12 OPRL 1 Crl:WI(Han).BN-OPRL1 1Hubr 19 p53 Knockout Crl:WI(UL)-Tp53 tm1/hubr 18 PCK PCK/CrljCrl-Prkhd1 pck /Crl 18 RIP-HAT CD:SD-Tg(ins2-IAPP)Soel 18 SERT WI(HAN)-Slc6a4 1Hubr /Crl 19 SHHF SHHF/MccGmiCrl-Lepr cp /Crl 18 SHR SHR/NCrl 16 Stroke Prone SHRSP/A3NCrl 19 WAG WAG/RijCrl 16 WISTAR Crl:WI 13 WISTAR Furth WF/lcoCrl 19 WISTAR HAN Crl:WI(Han) 13 WISTAR WU Crl:WI(WU) 14 WKY WKY/NCrl 16 ZDF ZDF-Lepr fa /Crl 17 ZSF1 ZSF1-Lepr fa Lepr cp /Crl 18 ZUCKER Crl:ZUC(Orl)-Lepr fa & Crl:ZUC-Lepr fa 17 MICE Common name Nomenclature Page S2/SvPasCrl 26 11BHSD2 C57BL/6NCrl-Tg(aMhc-Hsd11b2) 36 ApoE/J* B6.129P2-Apoe tm1unc /J 36 Athymic Nude Crl:NU(NCr)-Foxn1 nu 42 B6 Albino B6N-Tyr c /BrdCrCrl 32 B6C3F1 B6C3F1/Crl 33 B6CBAF1* B6CBAF1/J 33 B6D2F1/J* B6D2F1/J 34 B6D2F1/NCrl B6D2F1/NCrl 33 BALB/c NUDE CAnN.Cg-Foxn1 nu /Crl 39 BALB/c NUDE* CByJ.Cg-Foxn1 nu /J 39 BALB/cByJ* BALB/cByJ 27 BALB/cJ* BALB/cJ 26 BALB/cN BALB/cAnNCrl 27 BL/6J* C57BL/6J 29 BL/6N C57BL/6NCrl 29 Black Swiss Crl:NIHBL(SW) 23 C3H/HeOuJ* C3H/HeOuJ 28 C3H/N C3H/HeNCrl 28 CB6F1 CB6F1/Crl 34 CBA/Ca CBA/CaCrl 30 CBA/J* CBA/J 30 CD1 Crl:CD1(ICR) 21 CD2F1 CD2F1/Crl 34 Common name Nomenclature Page db* BKS.Cg-Dock7 m +/+Lepr db /J 35 DBA/1J* DBA/1J 31 DBA/2J* DBA/2J 31 DBA/2N DBA/2NCrl 31 Fox Chase Scid Crl:HA-Prkdc scid 42 Foxp3 C57BL/6J-Foxp3 tm1flv /Crl 37 FVB FVB/Ncrl 32 GLUT 4 C57BL/KsJ-db/db-Tg(SLC2a4)1Jdm 36 GSK3B FVB/N-Tg(Mic2-tTa-GSK3) 36 HSD11B1 FVB/N-Tg(AP2-HSD11b1) 36 IL4 C.129X1-Il4 tm1lky & B6.129X1-Il4 tm1lky /Crl LCAT C57BL/6J-Tg(Alb-LCAT)1Jdm 36 LOX-1 C57/BL6J-Tg(ORL1) 36 Ly5.1 B6.SJL-Ptprc a Pepc b /BoyCrl 37 MF1 Crl:MF1 21 MMP9 FVB/N-Tg(Eno2-MMP9) 38 NIH-III Crl:NIH-Lyst bg Foxn1 nu Btk xid 42 NMRCF1 NMRCF1/Crl 34 NMRI Crl:NMRI (Han) 22 NMRI nude Crl:NMRI-Foxn1 nu 42 NOD* NOD/ShiLtJ 36 NOD SCID* NOD.C.B-17-Prkdc scid /J 41 NSE-P25 FVB/N-Tg(Eno2-CDKSr1)1Jdm 38 NSG* NOD.Cg-Prkdc scid Il2rg tm1wjl /SzJ 41 NU/NU Crl:NU-Foxn1 nu 42 NUDE Crl:CD1-Foxn1 nu & Crl:NU(Ico)-Foxn1 nu 39 ob* B6.V-Lep ob /J 35 OF1 Crl:OF1 22 OT-I C57BL/6-Tg(TcraTcrb)1100Mjb/Crl 37 OT-II C57BL/6-Tg(TcraTcrb)425Cbn/Crl 37 PCSK9 C57BL/6J-Tg(ALB-PCSK9) 36 PGP Crl:CF1-Abcb1a mds 38 POUND MOUSE C57BL/6NCrl-Lepr db-lb /Crl 35 Rip-HAT FVB/N-Tg(Ins2-IAPP)RHF Soel 36 SCID C.B-17/lcr-Prkdc scid /lcrlcocrl 40 SCID BEIGE C.B-17.Cg-Prkdc scid Lyst bg-j /Crl 40 SHC CB17.Cg-Prkdc scid Hr hr /IcrCrl 42 SHO Crl:SHO-Prkdc scid Hr hr 40 SJL* SJL/J 32 SKH1 Crl:SKH1-Hr hr 23 RABBITS Common name Nomenclature Page New Zealand White Crl:KBL(NZW) 43 GUINEA PIGS Common name Nomenclature Page Dunkin Hartley Crl:HA 43 Hairless Guinea Pigs Crl:HA-Hr hr 43 HAMSTER Common name Nomenclature Page Syrian Hamster Crl:LVG(SYR) 44 GERBIL Common name Nomenclature Page Gerbil Crl:MON(Tum) *JAX Mice Strains 81

100 Charles River s 3Rs Charles River aims to reduce the number of research animals used by emphasizing health and genetic integrity to decrease study data variability. We also partner with customers to develop study designs decreasing the number of animals needed and suggesting pilot studies where appropriate. Replacement Any experimental system that does not entail the use of a whole, living animal is considered to be a replacement alternative. Reduction The concept of reduction alternatives covers any strategy that will result in fewer animals being used to obtain the same amount of information, or in maximizing the information obtained per animal and thus limiting or avoiding the subsequent use of additional animals. Refinement The term refi nement signifi es the modifi cation of any procedures performed on a laboratory animal to minimize the pain and distress experienced by the animal and to enhance its well-being.