Helping you. do research. better. Harlan Laboratories. UK Product Guide

Transcription

1 Helping you do research better Harlan Laboratories UK Product Guide Research Models and Services Effective December 2010

2 Harlan Laboratories Helping you do research better Models Harlan Laboratories is committed to the welfare and quality of our animal models as a top priority. We know this is important for the outcome of your research and the successful meeting of your institutional goals. Our veterinary, scientific, and quality staff are committed to ensuring our company mission helping you do research better. Learn more on Dale Cooper, DVM, MS, Dipl. ACLAM Director, Laboratory Animal Medicine, North America Diets Harlan Laboratories Teklad Diets have grown to be an industry leader by concentrating on reducing research variables through quality and consistency. Our nutritionists and production teams offer the expertise to ensure we help you do research better. Barb Mickelson, Ph.D. Nutritionist, Technical Services Services Harlan Laboratories services are focused on enhancing our support of your research activities. From surgical and custom animal projects to genetic testing services, we are dedicated to providing high quality services that help you meet your research needs. Amy Wineinger, BS,RVT,RLATG Manager, Technical Services 2

3 Contents Introduction 2 Harlan Worldwide Stocks and Strains Harlan Worldwide Research Model Services LABORATORY MICE Outbred Mice Inbred Mice THERAPEUTIC RESEARCH MODELS Oncology Mouse Models Athymic Nude 1 Contents Aged Mice Scid 1 Hybrid Mice 1 Rat Models Congenic Mice 1 Athymic Nude 0 Mutant Mice 1 Toxicology Rat Models LABORATORY RATS Sprague Dawley (SD) 21 Outbred Rats 21 Wistar Hannover 22 Inbred Rats 2 Rabbits 2 Aged Rats 2 Dogs Hybrid Rats 2 Mutant Rats 0 Diabetes Mouse Models Transgenic Rats 0 Obese ob/ob 20 Diabetic db/db 20 ADDITIONAL MODELS Rat Models Hamsters 1 Zucker fa/fa 0 Cotton Rats 1 Guinea Pigs 2 Rabbits 2 Dogs Biological Products and Services Contract Research Services Teklad Diets & Bedding Packing Guidelines 0 Microbiological & Genetic Monitoring 1 Surgical Services 2 Transgenic Services Colony Production and Maintenance Flexible Film Isolators Ordering Information Terms and Conditions tel + (0) fax + (0) 1 2 [email protected]

4 Harlan Worldwide Stocks and Strains Stocks and Strains United States United Kingdom The Netherlands France Israel Italy Mexico Japan Korea Page Outbred Rats Hsd:Sprague Dawley SD 21 HsdHot:Holtzman SD * Hsd:WI 2 HsdHan :WIST 22 RccHan :WIST 22 HsdOla:WI 2 HsdCpb:WU 2 HsdBlu:LE 2 HsdOla:LH 2 HsdCpb:ORGA 2 HsdHu:SABRAR * Inbred Rats ACI/SegHsd 2 BN/RijHsd 2 BN/SsNHsd 2 BN/SsNOlaHsd * BUF/SimRijHsd 2 DA/OlaHsd 2 F/NHsd 2 F/NCrHsd 2 LE/CpbHsd 2 LEW/Han Hsd 2 LEW/SsNHsd 2 LOU/MWslHsd 2 PVG/OlaHsd 2 SHR/NHsd 2 SR/JrHsd 2 SS/JrHsd 2 WAG/RijHsd 2 WF/NHsd 2 WKY/NHsd 2 Hybrid Rats* FBNF1/Hsd 2 Mutant Rats HsdHlr:ZUCKERLepr fa * HsdHlr:ZUCKERLepr fa /Lepr + * HsdHlr:ZUCKERLepr + * HsdOla:ZUCKERLepr fa 0 HsdOla:ZUCKERLepr fa /Lepr + 0 HsdOla:ZUCKERLepr + 0 Hsd:RHFoxn1 rnu 0 Hsd:RHFoxn1 rnu /Foxn1 + 0 United States United Kingdom The Netherlands France Israel Italy Mexico Japan Korea Page Outbred Mice CrlHli:CD1 * HsdWin:NMRI HsdIco:OF1 Hsd:ICR (CD1 ) Hsd:ND Hsd:NIHS Hsd:NSA (CF1 ) * HsdOla:MF1 HsdOla:TO HsdHu:SABRAM * Inbred Mice 12P2/OlaHsd 12 12S2/SvHsd 12 A/JOlaHsd 1 AKR/OlaHsd 1 BALB/cAnNHsd 10 BALB/cOlaHsd 10 BiozziABH/RijHsd 1 CBA/CaOlaHsd 1 CBA/JCrHsd * CBA/JHsd 1 CH/HeNHsd 12 CBL/NHsd CBL/JOlaHsd CBL/JRccHsd CBL/KaLwRijHsd 1 CBL/10ScNHsd * CBL/10ScSnOlaHsd 1 DBA/1OlaHsd 11 DBA/2NHsd * DBA/2OlaHsd 11 DBA/2JRccHsd 11 FVB/NHan Hsd 10 FVB/NHsd * NIH/OlaHsd 1 NZB/OlaHsd 1 NZW/OlaHsd 1 SAMP/TaHsd 12 SAMP/TaHsd 12 SAMR1/TaHsd (control) 12 SJL/JCrHsd * SJL/JHan Hsd 1 SJL/JOlaHsd 1 STR/OrtOlaHsd 1 Transgenic Rats Hsd:HIV1 (F) 0 Congenic Mice B10.R111H2 r /OlaHsd 1

5 Harlan Worldwide Stocks and Strains United States United Kingdom The Netherlands France Israel Italy Mexico Japan Korea Page Hybrid Mice* BCBAF1/OlaHsd 1 BCF1/Hsd * BCF1/OlaHsd 1 BD2F1/Hsd * BD2F1/OlaHsd 1 BD2F1/JRccHsd 1 CBF1/Hsd * CBF1/OlaHsd 1 CD2F1/Hsd 1 CSJLF1/HliHsd * NZBNZWF1/OlaHsd 1 United States United Kingdom The Netherlands France Israel Italy Mexico Japan Korea Page Rabbits HsdIf:NZW 2 HsdOkd:NZW * Hamsters HsdHan :AURA 1 Cotton Rats Hsd:Cotton Rat 1 Sand Rats HsdHu:Sand Rat * Stocks and Strains Mutant Mice B.VLep ob /OlaHsd 20 B.VLep ob /Lep + /OlaHsd 20 B.VLep + /OlaHsd 20 BALB/cJHan HsdPrkdc scid 1 BALB/cOlaHsdFoxn1 nu 1 BALB/cOlaHsdFoxn1 nu /Foxn1 + 1 BKS.Cg+ Lepr db /+ Lepr db /OlaHsd 20 BKS.CgDock m +/+ Lepr db /OlaHsd 20 BKS.CgDock m +/Dock m +/OlaHsd 20 C.B1/IcrHan HsdPrkdc scid 1 C.B1/IcrHsdPrkdc scid 1 C.B1/IcrHsdPrkdc scid Lyst bg 1 CH/HeJOlaHsdTlr Lpsd 1 CH.CPrkdc scid /IcrSmnHsd 1 CBL/Tyr c /BrdCrHsd 1 Hsd:Athymic NudeFoxn1 nu 1 Hsd:Athymic NudeFoxn1 nu /Foxn1 + 1 HsdCpb:NMRIFoxn1 nu 1 HsdCpb:NMRIFoxn1 nu /Foxn1 + 1 HsdHli:CD1Foxn1 nu * HsdIcr:Ha(ICR)Prkdc scid 1 Hsd:NIHSLyst bg Foxn1 nu Btk xid 1 Hsd:NIHSLyst bg Foxn1 nu /Foxn1 + Btk xid 1 HsdOla:ICRFFoxn1 nu 1 HsdOla:ICRFFoxn1 nu /Foxn1 + 1 HsdOla:MF1Foxn1 nu 1 HsdOla:MF1Foxn1 nu /Foxn1 + 1 HsdOla:T1Re 1 MRL/MpOlaHsdTnfrsf lpr 1 NOD.CB1Prkdc scid /NCrHsd 1 Guinea Pigs HsdPoc:DH 2 HsdDhl:DH 2 Consideration for maintenance and cryopreserved repository. Items Not Listed We invite inquiries about items not listed in this catalog. Our customer and technical service representatives are ready to discuss your special requirements. We will work with you to select the stocks and strains that best suit your needs. Dogs HsdCpb:DOBE(APD) HsdIf:DOBE HsdRcc:DOBE Cats HG:KUN(APD) * Cryopreserved Strains Inbred Rats AO/OlaHsd AUG/OlaHsd BDIX/Han Hsd LOU/CNimrOlaHsd LUDW/OlaHsd Mutant Rats HsdOla:DWARFdw Congenic Rats PVG.DART1 av1 /OlaHsd PVG.AORT1 u /OlaHsd PVG.R/OlaHsd Inbred Mice BALB/cByJHan Hsd MRL/MpOlaHsd SWR/OlaHsd Outbred Mice HsdCpb:SE HsdWin:CFW1 Mutant Mice CBL/OlaHsdLyst bg CBL/OlaHsdWld S CBA/HNOlaHsdBtk xid HsdOla:MF1HR hr Congenic Mice B10.AH2 a /OlaHsd B10.AH2 h2 /OlaHsd B10.AH2 h /OlaHsd B10.AH2 k /OlaHsd B10.AH2 d /nolahsd B10.AH2 s /nolahsd B10.D2H2 d /nolahsd B10.GH2 q /OlaHsd B10.CgH2 f /OlaHsd B10.SH2 i /OlaHsd C.B10H2 b /OlaHsd C.CHH2 k /OlaHsd CBL/Han HsdIgh1 a Han is a trademark of Harlan Laboratories, Inc., Indianapolis, Indiana, USA. Sprague Dawley SD and Holtzman are U.S. registered trademarks of Harlan Laboratories, Inc., Indianapolis, Indiana, USA, and trademarks of Harlan Laboratories, Inc., in the United Kingdom. NSA is a trademark of Harlan Laboratories, Inc., Indianapolis, Indiana, USA. CD1, CF1, CFW and CD are registered trademarks of Charles River Laboratories, Wilmington, Massachusetts, USA. FOX CHASE SCID is a trademark of the Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. * This is a brief selection of available hybrids; any combination can be bred on demand; for the same reason, any existing hybrid combination can be discontinued at any time without prior notice. tel + (0) fax + (0) 1 2 [email protected]

6 Harlan Worldwide Research Model Services Research Model Services Teklad Global Diets and Bedding Standard Diets (pelleted and extruded) Autoclavable Diets Irradiated Diets Certified Diets Medicated Diets Custom Research Diets Bedding Cage Enrichment Cage Liners Preconditioned Models Aging Research Models Animal Model Development Animal Identification (tattooing, implantation etc.) Diabetic Induced Models (STZ induced) Diet Induced Obesity Models Feeding Studies Genetic Testing Services Standard PCR Zygosity Testing Inbred Strain Verification Gene Expression Speed Congenics Prevalidated SNP Zygosity Testing Prevalidated Reporter and Conditional Model Testing Surgical Services Surgical Services Surgical Training Courses in Rodents Surgical Training Courses in Large Animals Health Monitoring Serology Bacteriology Parasitology Pathology Molecular Biology Biological Products Serum Fetal Bovine Serum Plasma Compliment Tissues, Organs, Glands Whole Embryo Culture Serum EGF, 2.S and.0s Nerve Growth Factor Cytokines United States United Kingdom The Netherlands France Israel Italy Spain Switzerland Germany Processing and Cell Line Services Bioburden Testing Endotoxin Testing Sterility Testing Subcloning Cell Banking Cell Line Sterility Cell Line Viability Testing Mycoplasma Cleanup Cell Weaning Cell Recovery Cell Line Isotyping IgG Concentration Testing Custom Antibody Production cgmp In Vivo Production (Diagnostic and Therapeutic Use) NoncGMP In Vivo Production () In Vitro Monoclonal Antibody Production (cgmp and ) Research Scale In Vitro Monoclonal Production Hybridoma Development Polyclonal Antibody Production Mouse Antibody Production (MAP) Testing Antibody Purification Fragmentation / Conjugation Colony Management Services Maintenance Research Models Contract Breeding Import / Export Services Quarantine Facility Services Facility management Containment Solutions (Isolators) Transgenic Services Embryotransfer Cryopreservation Revitalisation Spermcell freezing ES Cell development Contract Research Services (see page for further details) Nonclinical CRO services United States United Kingdom The Netherlands France Israel Italy Spain Switzerland Germany Although the above Research Model Services are listed by location, these are globally available. Items Not Listed We invite inquiries about services not listed in this overview. Our technical service representatives are ready to discuss your special requirements. We will work with you to select the services that best suit your needs.

7 ICR(CD1 ) TO Hsd:ICR (CD1 ) price per animal ( ) 110 2, 111,10 120,20 212,2 20,0 1,0 +, 2,,1,1 Littermates 21 days old,0 Weekend Mating Charge,0,00 2,0 Isochip 1,0 HsdOla:TO price per animal ( ) ,2,0,0,0,,0,0 2,,1,1 11,,0 * For our pregnancy policy, refer to page. Albino. Stock developed at Statens Serum Institute, Denmark. In 10 to Clinical Research Centre, Harlow and to Olac (now Harlan Laboratories) in 1 Outbred Mice * For our pregnancy policy, refer to page. Albino. Derived from animals from Charles River Laboratories, Wilmington, Massachusetts. Litter average: 11. Docile disposition Most widely used outbred mouse Excellent reproductive and maternal characteristics High incidence of retinal degeneration (Pdeb rd1 ) General purpose Surgical Models Diet Induced Models Sensitised Models Oncology Vaccines Teratology Additional Available Data Hematology 2 year growth and survival Surgical Models Sensitised Models Toxicology Aging General purpose Clinical chemistry Organ weights Diet Induced Models ICR Harlan Laboratories maintains a range of mouse stocks and strains, free of opportunistic bacteria to include; Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus aureus and Proteus spp. Contact your Customer Service Department for additional information. Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. tel + (0) fax + (0) 1 2 [email protected]

8 MF1 NIH Swiss Outbred Mice HsdOla:MF1 price per animal ( ) 110,00 111,0 120,20 212,0 20, 1+,0 1,,20,20 11,0,0 Hsd:NIHS price per animal ( ) 110,0 111,0 120, 212,0 20, 1+,,0,, 1,,0 * For our pregnancy policy, refer to page. Albino. Developed at Olac, United Kingdom (now Harlan Laboratories), prior to 10 from a cross between mice of a Swiss background. * For our pregnancy policy, refer to page. Albino. Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, USA. Surgical Models Sensitised Models Diet Induced Models MF1 General purpose Surgical Models Diet Induced Models Sensitised Models Additional Stocks of Outbred Mice price per animal ( ) Stock Hsd:ND HsdIco:OF1 HsdWin:NMRI,1,,20 Over weeks, add per week 0,0 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Harlan Laboratories maintains a range of mouse stocks and strains, free of opportunistic bacteria to include; Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus aureus and Proteus spp. Contact your Customer Service Department for additional information.

9 CBL/ CBL/ CBL/JOlaHsd CBL/JRccHsd CBL/NHsd price per animal ( ),10,0, 10,00 11,0 12,0 1,0 Over weeks, add per week 1,,0,, Littermates 21 days old 11,0 Weekend Mating Charge,0 1,,0 Isochip 1,0 * For our pregnancy policy, refer to page. Black. CBL/JOlaHsd mice originate from the Jackson Laboratory, Bar Harbor, Maine. In 1 to the Laboratory Animal Centre, Carshalton UK. To Olac in 1 (now Harlan Laboratories). CBL/NHsd; Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. The CBL/JRccHsd mice originate from Jackson Laboratory, Bar Harbor, Maine and were moved in 1 to RCC Ltd. (formerly Ibm and BRL) in Füllinsdorf, Switzerland. To Harlan Laboratories through acquisition in 200. Litter average:. Haplotype: H2 b Most widely used inbred strain Low tumor incidence High preference for alcohol Microphthalmia Incidence of Hydrocephalous The CBL/JRccHsd subline does not carry the Nnt (nicotinamide nucleotide transhydrogenase) gene deletion The CBL/JOlaHsd subline carries a deletion at the alpha synuclein locus Background for induced and genetically modified models Diet induced obesity Toxicology Aging Cardiovascular Superovulation Immunology Drug addiction Alcoholism General purpose Additional Available Data Hematology Clinical chemistry Surgical Models Sensitised Models Diet Induced Models Aged Mice Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Cohorts of the below listed female mice are reserved each month for the intended purpose of providing aged animals for research. Pricing of aged animals from inventory is listed below. If the requested aged animals are not available from our inventory, Harlan will age animals to accommodate your research requirements. When planning for your aged animal requirements, please consider the need to reserve extra animals on your order to replace any losses due to natural causes. CBL/JRccHsd price per animal ( ) Age (months) 2, 2,0 0,,0,, 2, 10 0,0 11, 12,0 1 10, 1 11,0 1 12,10 1 1, 1 1,0 1 1,0 1 1, 20 10, 21 1, , 2 21,0 2 21,0 tel + (0) fax + (0) 1 2 [email protected] Inbred and Aged Mice

10 Inbred Mice BALB/c BALB/cAnNHsd BALB/cOlaHsd price per animal ( ) Over weeks, add per week * For our pregnancy policy, refer to page. Albino. BALB/cOlaHsd mice originate from the Laboratory Animal Centre, Carshalton UK from the Jackson Laboratory, Bar Harbor, Maine in 1. In 1 to Olac (now Harlan Laboratories). BALB/cAnNHsd; Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. Litter average:.0 Haplotype: H2 d Cardiovascular Toxicology Aging General purpose Additional Available Data Hematology Docile disposition Experimental allergic encephalomyelitis resistant Monoclonal antibody production Pharmacology Teratology Clinical chemistry,,,,0 10, 11,0 1,0 1, 0,0 0, 0, 11,1,0 FVB FVB/NHan Hsd price per animal ( ), 11, 1,00 1,0 1, 1,1 1, Over weeks, add per week 1,0,0 2,0,00 1,, * For our pregnancy policy, refer to page. Albino. Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland, in 1. In 1 to Harlan Laboratories through acquisition of Central Institute for Laboratory Animal Breeding (ZfV), Hannover, Germany. Surgical Models Diet Induced Models Sensitised Models FVB Surgical Models Sensitised Models Diet Induced Models BALB/c Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. 10 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Harlan Laboratories maintains a range of mouse stocks and strains, free of opportunistic bacteria to include; Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus aureus and Proteus spp. Contact your Customer Service Department for additional information.

11 DBA/2 DBA/1 DBA/2OlaHsd DBA/2JRccHsd price per animal ( ) 11, 12,0 1,2 1, 1, 1,0 1,00 Over weeks, add per week 1,0, 0,0,0 20,0 10,0 * For our pregnancy policy, refer to page. Dilute brown, nonagouti. Originally developed by Little. Acquired by Laboratory Animal Centre, Carshalton UK. In 12 to Olac (now Harlan Laboratories). The DBA/2JRccHsd mice originate from Jackson Laboratory, Bar Harbor, Maine and were moved in 1 to RCC Ltd. (formerly Ibm and BRL) in Füllinsdorf, Switzerland. To Harlan Laboratories through acquisition in 200. Litter average:. Haplotype: H2 d Dystrophic myocardial calcinosis Progressive hearing loss Audiogenic seizures Surgical Models Diet Induced Models Sensitised Models DBA/1OlaHsd price per animal ( ) 12,0 1, 1, 1,1 1, 21, 2,0 Over weeks, add per week 2,00,, 10,0 2, 1, * For our pregnancy policy, refer to page. Dilute brown, nonagouti. Originally developed by Little. Acquired by Laboratory Animals Centre, Carshalton, United Kingdom in 1; to Olac (now Harlan Laboratories) in 1. Litter average:. Haplotype: H2 q Adjuvantinduced arthritis Immunology Inflammation Surgical Models Diet Induced Models Sensitised Models Inbred Mice DBA/2 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. tel + (0) fax + (0) 1 2 [email protected] 11

12 CH 12 Inbred Mice CH/HeNHsd price per animal ( ),00,10,0,0 10, 12,0 1, Over weeks, add per week 1,,0,0,10 1,,00 12P2/OlaHsd 12S2/SvHsd price per animal ( ),1 1,,00,0,0,0 2, Over weeks, add per week 1,0 Pinkeyed, light bellied chinchilla. 12P2/OlaHsd; Developed by Dunn in 12 from a cross of coat color stocks and a chinchilla stock from Castle. Light bellied, agouti. 12S2/OlaHsd; Developed by Dunn in 12 from a cross of coat color stocks and a chinchilla stock from Castle. * For our pregnancy policy, refer to page. Agouti. Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. Litter Average:.0 Haplotype: H2 k Carrier of the retinal degeneration (Pdeb rd1 ) mutation Normal response to LPS Highly susceptible to Anthrax toxin General Purpose Ocular Disease Immunology Additional Available Data Clinical chemistry Hematology Surgical Models Diet Induced Models Sensitised Models Low overall tumour incidence (P2) Low blood pressure (P2) High incidence of testicular teratomas (P2) High incidence of urinary calculi (P2) Histocompatibility: H1 b, H2 b, H b (P2) Low preference for sweet tasting substances (S2) Used in the production of targeted mutations due to the availability of several lines of embryonic stem cells. (P2, S2) Ovary transplant and ova transfer studies (P2) Used in gene targeting studies (S2) SAM SAMP/TaHsd SAMP/TaHsd SAMR1/TaHsd (control) price per animal ( ) 11,20 1,10 12,0 11, Over weeks, add per week,0 CH Albino. SAM models were developed from AKR/J by Kyoto University. Five litters with severe senescence were selected to further propagate and examine these characteristics. Litters that showed normal aging were selected as a senescenceresistant series (Rseries). The genetic background of the SAM mice became suspect after the pathological findings were different from the AKR/J mouse. Each SAM model is genetically different. Each SAM colony was acquired by Harlan from Takeda Chemical Ltd. in Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Accelerated senescence studies Aging process Geriatric pathogenesis Agedependent disorders Senile amyloidosis (apolipoprotein AII) Senile osteoporosis Impaired immune response Hyperinflation of the lungs Hearing impairment Deficits in learning and memory Emotional disorders Brain atrophy General purpose model Surgical Models Diet Induced Models Sensitised Models 12

13 CBA/Ca NIH CBA/CaOlaHsd price per animal ( ),0,20 10,0 11,0 1,0 1,0 1, Over weeks, add per week 1,,1,, 1,, NIH/OlaHsd price per animal ( ),,0,0 10,1 11, 12, 1, Over weeks, add per week 1,0,00,00,00 10,0, Inbred Mice * For our pregnancy policy, refer to page. Agouti. Obtained by the Laboratory Animal Centre, Carshalton UK from Atomic Energy Establishment, Harwell in 1 and then to Olac in 1 (now Harlan Laboratories). * For our pregnancy policy, refer to page. Albino. From Burroughs Welcome to Olac (now Harlan Laboratories) in 1 Surgical Models Diet Induced Models Sensitised Models Surgical Models Diet Induced Models Sensitised Models Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. CBA/Ca Additional Strains of Inbred Mice Strains A/JOlaHsd *AKR/OlaHsd BiozziABH/RijHsd CBA/JHsd CBL/10ScSnOlaHsd CBL/KaLwRijHsd *NZB/OlaHsd NZW/OlaHsd SJL/OlaHsd SJL/JHan Hsd *STR/OrtOlaHsd Over weeks, add per week price per animal ( ) * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. 10, 1,0 2,,2,0 1,0, 2,0 2,0 1,,0 2, Harlan Laboratories maintains a range of mouse stocks and strains, free of opportunistic bacteria to include; Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus aureus and Proteus spp. Contact your Customer Service Department for additional information. tel + (0) fax + (0) 1 2 [email protected] 1

14 CD2F1 BCBAF1 Hybrid Mice CD2F1/Hsd price per animal ( ) 1, 1,1 1, 1, 22,0 2,0 2,0 Over weeks, add per week 2,0 1,0 2,0 2,0 BCBAF1/OlaHsd price per animal ( ) 1,0 1,0 1,0 21,00 2,1 2, 2,0 Over weeks, add per week 2,2 0,,, * For our pregnancy policy, refer to page. Beige. Offspring of a cross between the BALB/cAnNHsd inbred female and the DBA/2NHsd inbred male. * For our pregnancy policy, refer to page. Agouti. Offspring of a cross between the CBL/JOlaHsd inbred female and the CBA/CaOlaHsd inbred male. Surgical Models Diet Induced Models Sensitised Models Surgical Models Diet Induced Models Sensitised Models CBF1 CBF1/OlaHsd price per animal ( ) CD2F1 Over weeks, add per week 1,0 1,0 1, 20, 22,0 2,1 2,0 2,20,2,00,0 * For our pregnancy policy, refer to page. Agouti. Offspring of a cross between the BALB/cOlaHsd inbred female and the CBL/JOlaHsd inbred male. Surgical Models Diet Induced Models Sensitised Models BCBAF1 CBF1 1 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet.

15 BCF1 BD2F1 BCF1/OlaHsd price per animal ( ) 12, 1, 1, 1, 20,0 22,0 2, Over weeks, add per week 2,0,00,2 0,0 * For our pregnancy policy, refer to page. Agouti. Offspring of a cross between the CBL/JOlaHsd inbred female and the CH/HeNHsd inbred male. Surgical Models Diet Induced Models Sensitised Models BD2F1/OlaHsd BD2F1/JRccHsd price per animal ( ) Over weeks, add per week * For our pregnancy policy, refer to page. Black. Offspring of a cross between the CBL/JOlaHsd inbred female and the DBA/2OlaHsd inbred male. The BD2F1/JRccHsd mice are offspring from a cross between the CBL/JRccHsd inbred female and the DBA/2JRccHsd inbred male. Surgical Models Diet Induced Models Sensitised Models 10, 11,10 12,0 1,1 1, 1,0 1,0 2,00,10,0, Hybrid and Congenic Mice BCF1 BD2F1 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Additional Strains of F1 Hybrid Mice price per animal ( ) Strain *NZBNZWF1/OlaHsd Over weeks, add per week 1,2 2, Congenic Mice Strains B10.R111H2 r /OlaHsd Over weeks, add per week price per animal ( ), 12,0 This is a brief selection of hybrid mice; any combination can be bred on demand. * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. For the same reason, any existing hybrid combination can be discontinued at any time without prior notice. tel + (0) fax + (0) 1 2 [email protected] 1

16 At Harlan Laboratories, we have passion for oncology research and share in your dedication to curing cancer. Our Research Models and Services group advances your efforts by providing mice and rats specifically bred for oncology research. We recognize the specialisation involved in the field of oncology research and we have the global resources to meet your needs Mutant Mice 1 Your Oncology Partner Strong history of quality models with defined health status Comprehensively screened for viruses, fungi, parasites, and commensal and pathogenic bacteria Variety of research tested models supported by extensive references Access to multiple models Excellent record of tumor uptake Extensive technical support Cell line and model literature search Surgically modified animals Teklad diets and bedding Custom antibodies Global availability Inventory available to support regional and worldwide research collaborators Teklad Global Rodent Diets (page ) Reducing research variables A range of global diets for all aspects of your oncology research Minimal phytoestrogens Reduces influence on tumor growth No alfalfa meal Improves optical imaging clarity with the absence of chlorophyll No animal byproducts nitrosamines are virtually eliminated Questions: [email protected] Custom Antibodies Standard and custom protocols Quick scaleup Reproducibility Cell line optimization Questions: [email protected] Visit us at for our full portfolio on oncology products and services or ask for our oncology brochure Oncology models with proven performance for cell lines Choosing the right model for your research. Below you will find a representation of the cell lines used successfully with Harlan Laboratories models. For access to a full listing and our references, please visit Cell Lines Bladder T2 Brain G HTLA20 SHSYY U21NG2 UMG U UFluc U21 Breast MCF MDAMB21 MT1 TD MDAMB1 BT LS1T MEFpHER2 JIMT1 Cervical HeLa Colon CT2 CX1 DLD1 HCA HCT11 HT2 Fibrosarcoma HT100 Gastric Carnicoma N Glioma C UMG Head / Neck FaDu HNXOE WSUHN1 Cal2 UMscc1 CCL 2 Leukemia/Lymphoma BW1 Grant 1 HPBALL Karpas 2 nude mice scid mice nude rats L0cy HL0 HEL21 TF1 AML Liver HepT1 HepB HuH Lung A Colo H22 H KNS2 LL2 NCIH0 NCIH1 BEN Melanoma B1F10 MDAMB SIT1 TAC ZAZ NIH12 DM Ovarian MOT OVCAR SKOV CAOV OVA1 NMP1 Pancreas CFPAC1 Colo MiaPaCa2 PANC1 Panc PL Prostate CWR22 DU1 LNAI PC Testicular NCCIT Multiple Myeloma LAG 1 KAS/1 nude mice scid mice nude rats

17 *BALB/c Nude *MF1 Nude BALB/cOlaHsdFoxn1 nu price per animal ( ) nu/nu nu/+ Over weeks, add per week,0, 1,,0,1,20,0 2,10 1, 1, 20, 22, 2, 2,2 2,0 2, 110, 1, 1,2 HsdOla:MF1Foxn1 nu price per animal ( ) nu/nu nu/+ Over weeks, add per week 0,1 1,0,,2,0 1,1, 2,0 1, 1, 21, 2, 2,20 2,0 1,1 2,2,0 0,20 1,0 Mutant Mice Albino. Institute of Animal Genetics, Edinburgh to Laboratory Animals Centre, Carshalton, to GD Searle, High Wycombe, to Olac (now Harlan Laboratories) in 1 Albino. Institute of Animal Genetics, Edinburgh to Laboratory Animals Centre, Carshalton, to Olac (now Harlan Laboratories) in 12 on mixed background. Backcrossed to HsdOla:MF1 mice *ICRF Nude HsdOla:ICRFFoxn1 nu price per animal ( ) nu/nu nu/+ Over weeks, add per week 0,0 2,0,,1 1,0,0,,20 22, 2,0 2,0 0,,0,0,0,20 P.O.R. P.O.R. P.O.R. Albino. Institute of Animal Genetics, Edinburgh to Laboratory Animals Centre, Carshalton. From Imperial Cancer Research Fund, South Mimms to Olac (now Harlan Laboratories) in 1 The nu allele on chromosome 11 is an autosomal recessive mutation Dysfunctional rudimentary thymus Phenotypically hairless (sparse hair growth possible) Tcell deficient Bcells function normal No generation of cytotoxic effector cells No graft versus host response Foxn1 nu /Foxn1 + heterozygotes do not show partial expression of the nu phenotype Oncology Transplantation Tumor cell growth Immunology Autoimmune disease Antibody production Sentinel model heterozygous Foxn1 nu /Foxn1 + Additional Available Data Hematology Clinical chemistry Proven models with extensive references (see page 1) Surgical Models Diet Induced Models Sensitised Models * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. tel + (0) fax + (0) 1 2 [email protected] 1

18 *FOX CHASE SCID *FOX CHASE SCID /Beige Mutant Mice C.B1/IcrHan HsdPrkdc scid C.B1/IcrHsdPrkdc scid HsdIcr:Ha(ICR)Prkdc scid price per animal ( ) Over weeks, add per week 0, 2,10,,,0,0 0,00 1,0 Albino. Harlan acquired from the Fox Chase Cancer Center, Philadelphia, Pennsylvania, in 11. FOX CHASE SCID is a registered trademark of Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. C.B1/IcrHsdPrkdc scid Lyst bg price per animal ( ) 2,,10,,,0 0,0 2, Over weeks, add per week 1, Albino. Harlan acquired from the Fox Chase Cancer Center, Philadelphia, Pennsylvania, in 11. FOX CHASE SCID is a registered trademark of Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. BALB/cJHan HsdPrkdc scid CH.CPrkdc scid /IcrSmnHsd price per animal ( ),1 0,1 1,,2,1,0,0 Over weeks, add per week 2,1 Albino or Agouti. Harlan acquired from the Fox Chase Cancer Center, Philadelphia, Pennsylvania, in 11. FOX CHASE SCID is a registered trademark of Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. Autosomal recessive, single nucleotide polymorphism within Prkdc gene on chromosome 1 Autosomal recessive, beige mutation on chromosome 1 Severe combined immunodeficiency affecting T and B cell development Severe lymphopenia Diminished Natural Killer (NK) cell activity relative to other SCID models Rudimentary thymus Leaky phenotype significantly suppressed relative to other SCID models Highly susceptible to opportunistic viral and bacterial infection Oncology Teratology Transplantation Tumor cell growth Immunology Autosomal recessive, single nucleotide polymorphism within Prkdc gene on chromosome 1 Severe combined immunodeficiency affecting T and B cell development Natural Killer (NK) cell, macrophage and granulocyte cell numbers and function are normal As SCID mice age, a variable percentage become leaky from the spontaneous development of functional T and B lymphocytes Highly susceptible to opportunistic viral and bacterial infection Oncology Tumor cell growth Transplantation Immunology Additional Available Data Proven models with extensive references (see page 1) Surgical Models Sensitised Models Diet Induced Models Visit us at for our full portfolio on oncology products and services or ask for our oncology brochure 1

19 *NOD SCID CBL/ (Albino) NOD.CB1Prkdc scid /NCrHsd price per animal ( ),1 0,1 1,,2,1,0,0 Over weeks, add per week 2,1 Albino. Received by National Cancer Institute, Frederick, Maryland in 200 from National Institutes of Health, Bethesda, Maryland. Harlan Laboratories acquired from National Cancer Institute in 200. * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. CBL/Tyr c /BrdCrHsd price per animal ( ) 1,0 1, 1, 1,0 1,0 21,2 2, Over weeks, add per week 2,20 2, 10, 1, 1,1 11,0 Mutant Mice Autosomal recessive, single nucleotide polymorphism within Prkdc gene on chromosome 1 Severe combined immunodeficiency affecting T and B cell development Natural Killer (NK) cell, macrophage and granulocyte cell numbers and function are reduced As SCID mice age, a variable percentage become leaky from the spontaneous development of functional T and B lymphocytes Highly susceptible to opportunistic viral and bacterial infection Development of autoimmune diabetes does not occur due to severe combined immunodeficiency High incidence of thymic lymphomas Oncology Tumor cell growth Transplantation Immunology Additional Available Data Hematology 12 week growth Proven models with extensive references (see page 1) SHrN TM (SCID Hairless NOD) Coming Soon To get information, visit * For our pregnancy policy, refer to page. Albino. From Allan Bradley at Baylor College of Medicine to National Cancer Institute (NCI) in 2000; to Harlan in 200. Litter average:. Haplotype: H2 b Contains a mutation in the c (tyrosinase) gene Source of albino CBL/ embryos for chimera generation Ovarian transfer Surgical Models Sensitised Models Diet Induced Models Additional Stocks and Strains of Mutant Mice Strain CH/HeJOlaHsdTlr Lpsd *MRL/MpOlaHsdTnfrsf lpr *Hsd:Athymic NudeFoxn1 nu Hsd:Athymic NudeFoxn1 nu /Foxn1 + *HsdCpb:NMRIFoxn1 nu HsdCpb:NMRIFoxn1 nu /Foxn1 + HsdOla:T1HRe *Hsd:NIHSLyst bg Foxn1 nu Btk xid Hsd:NIHSLyst bg Foxn1 nu /Foxn1 + Btk xid Over weeks, add per week price per animal ( ) * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. 2,0 1,0 1, 11,20 2, 1,,2,,,1 tel + (0) fax + (0) 1 2 [email protected] 1

20 *Obese (ob/ob) *Diabetic (db/db) Mutant Mice B.VLep ob /OlaHsd price per animal ( ) ob/ob lean** Over weeks, add per week,0, 1,0,0,2,00 2, 2, 0,0,0, 2, P.O.R. P.O.R. P.O.R. Black. Mutation backcrossed onto the CBL/J strain at The Jackson Laboratories, Bar Harbor, Maine, in the 10 s. Acquired by the Laboratory Animals Centre, Carshalton, United Kingdom, in 1. To Olac, United Kingdom, in 1. To Harlan Laboratories, in Additional Related Genotypes: B.VLep ob /Lep + /OlaHsd, B.VLep + /OlaHsd * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. ** Genetic testing is required to determine Lep ob /Lep + or Lep + genotype. See page 1 for genotyping services available from Harlan Laboratories. BKS.Cg + Lepr db /+ Lepr db /OlaHsd price per animal ( ) db/db lean** Over weeks, add per week,0,10,1 2,,0 2,0 2,10 2,2 2,,,0 2,0 P.O.R. P.O.R. P.O.R. Black or misty. From Dunn Nutritional Laboratory, Cambridge, United Kingdom; to Olac, United Kingdom, in 1; to Harlan Laboratories, in Additional Related Genotypes: BKS.CgDock m +/+ Lepr db /OlaHsd (black, lean) BKS.CgDock m +/Dock m +/OlaHsd (misty, lean) * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. ** Our breeding scheme maintains m and Lepr db in repulsion. These genes are closely linked; however, recombination could occur. Our mice are most likely nonrecombinants, but they have not been tested. See page 1 for genotyping services available from Harlan Laboratories. Lep ob is an autosomal recessive mutation on chromosome Exhibit obesity around weeks of age Hyperphagia Hyperinsulinemia Transient moderate hyperglycemia Hyperlipemia Leptin protein deficient Insulinresistant Defective body temperature regulation Adipocyte hyperplasia Sterile homozygous females Lepr db is an autosomal recessive mutation on chromosome Obesity expressed around weeks of age Elevation of plasma insulin demonstrated at 101 days Onset of hyperglycemia expressed at weeks of age Polyphagia Proteinuria Glycosuria Polyuria/ Polydipsia Hyperinsulinemia despite severe depletion of pancreatic islet insulinproducing Bcells Leptin receptor deficient Obesity Diabetes, Type II Metabolism Gerontology Nutrition Additional Available Data Hematology Clinical chemistry 12 week growth Surgical Models Diabetes, Type II Peripheral neuropathy Myocardial disease Immunodeficiency Immunology Metabolism Obesity Additional Available Data Hematology Clinical chemistry 12 week growth Glucose tolerance test Surgical Models 20

21 Sprague Dawley Hsd:Sprague Dawley SD price per animal ( ) Male Female Over 10 weeks, add per week Littermates 21 days old Weekend Mating Charge Isochip,,0,0,0, 10,2 11,20 12,2 1,0 1,0 1,0 1, 1,10 2,20 12, 1,0,0 1,0,0,0,0,1, 10, 12,10 1,0 2,,0,0,0 12,, 2,0,20 1,0 * For our pregnancy policy, refer to page. Albino. Originated by the SpragueDawley Company in 12 through a series of crosses begun with a singlehooded male and six albino females of unknown origin. Current Harlan Laboratories colonies are direct descendants of this original colony. Learn more about our Surgical Services. See Page 2. SPRAGUE DAWLEY Outbred Rats Most widely used outbred rat in animal research Litter average: 11.0 Docile disposition Excellent reproductive performance and maternal characteristics Toxicology Aging Teratology Oncology Nutrition Dietinduced Obesity General purpose Survival (%) Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Additional Available Data Hematology Clinical chemistry Neoplastic and nonneoplastic lesions 10 week growth and survival Surgical Models Diet Induced Models Sensitised Models Aging available for SD rats tel +1 (0) 00 fax +1 (0) [email protected] 21

22 The RccHan :WIST improves toxicology outcomes Outbred Rats longer survival reduced cost, improved study outcomes smaller body size less compound and cost lower spontaneous tumor incidence reduced research variables, improved animal welfare global breeding and monitoring system consistent research outcomes Longer Survival Survival Comparison Between Rat Strains (10 weeks)* RccHan TM :WIST Male RccHan TM :WIST Female Crl:CD (SD) Male Crl:CD (SD) Female Over 0% survival at 10 weeks of age. Longevity of the RccHan :WIST ensures study completion with confidence Smaller body size Up to 2% lighter weight in twoyear studies without restricting diet compared to the leading US 1 model. Body Weight Comparison Between Rat Models (10 weeks)* Crl:CD (SD) Male RccHan TM :WIST Male Crl:CD (SD) Female Lower spontaneous tumor incidence Overall tumor incidence of common tumor types at 10 weeks is significantly lower in the RccHan TM :WIST. Reduced attrition due to spontaneous lesions Spontaneous Tumor Incidence* RccHan TM :WIST Male RccHan TM :WIST Female Crl:CD (SD) Male Crl:CD (SD) Female RccHan TM :WIST Female Ultimate benefits: Cost savings Less compound use Fewer animals Reduced labor Fewer animals Housing efficiency No need for diet restriction 1% lower food consumption compared to leading US model 1 Reduced research variables Fewer background lesions to evaluate More robust data due to longer survival Twenty years of historical background data for comparative evaluation Improved animal welfare Fewer animals needed at study start Smaller body size allows pair housing in standard size caging Lower tumor incidence * RccHan :WIST data compiled from 0 studies performed at Harlan Laboratories Switzerland from , n = 12 males, n=11 females, animals, Crl:CD (SD) data compiled from 1 studies, 1 Hooks, W.M. (2001) A Review of the Mortality, Body Weight and Food Consumption Data from CD (SD) IGS Rat Tumorigenicity Studies Completed in 1 to 2001, Huntingdon Life Sciences, Huntingdon, UK, 2001:

23 Wistar Han RccHan :WIST HsdHan :WIST price per animal ( ) Male Female Over 12 weeks, add per week Littermates 21 days old Weekend Mating Charge Isochip,0,0,,20 10,1 10,0 12,00 1,10 1,20 1, 1,0 1,0 1,0 2,0 12, 21,,2 1,,0,,, 10,0 11, 12,0 1,20 2,0,20,0,0 12,,00 21,,0 1, * For our pregnancy policy, refer to page. Albino. Derived at Biological Research Laboratories Limited (BRL), formerly RCC, now Harlan Laboratories Ltd., Füllinsdorf, Switzerland from original colony at Zentralinstitute für Versuchstierzucht, Hannover in 1. Transferred to Harlan SpragueDawley, Inc., now Harlan Laboratories in 1 (nomenclature HsdHan :WIST). In 200 Harlan acquired RCC Ltd. and new breeding stock was transferred in 200 (nomenclature RccHan :WIST). As a result of this Harlan will replace all HsdHan :WIST colonies with RccHan :WIST stock in accordance with the Harlan Global Models Breeding System procedures. Unlike competitive models, the RccHan :WIST rat has been maintained from the original nucleus of 1 breeding pairs in Hannover, Germany. Toxicology Oncology Teratology Aging General purpose Surgical Models Sensitised Models 20 Years of Stable Control Data on Diet Induced Models Aging available for Wistar Han rats Acute to Oncogenicity studies,,12 and 2 months Survival rates Growth Food and water consumption Clinical Observations Functional Observation Battery Ophthalmoscopy Clinical Pathology P0 Enzymes Gross Lesions and Organ Weights Bone Marrow Differentiation Incidence and images of spontaneous neoplastic and nonneoplastic changes Reproductive and developmental data Outbred Rats WISTAR Han (RccHan :WIST) Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Millions of data points to compare to your research to validate the RccHan :WIST as the model of choice! Visit tel + (0) fax + (0) 1 2 [email protected] 2

24 Long Evans Lister Hooded Outbred Rats HsdBlu:LE price per animal ( ) Male Female ,10 1,0 1,10 1,1 20, 22,0 2, 2, 2,0 1,10,20,0,1 1,0 2, 1,10 1,0 1,10 1,00 21,0 2, 2,20 2,,,2,0 1,0 2, HsdOla:LH price per animal ( ) Male Female ,2,10,,0 10, 11, 12, 1,0 1, 1, 1,00 1,20 20,10 20,,00,2,10,0,0 11,00 12,0 1, 1,00 0,0,0 0, 20,,00 * For our pregnancy policy, refer to page. Blackhooded. From the University of Rochester, Rochester, New York; to Blue Spruce Farms, Altamont, New York, in 1; to Harlan through acquisition in 1. * For our pregnancy policy, refer to page. Blackhooded. From ICI, Alderley Edge in 12 to Medical Research Council, Mill Hill, UK. In 1 to Olac (now Harlan Laboratories). Litter average: 10 Individual housing of males recommended Good maternal characteristics Litter Average: 10.0 Disposition: Docile Slow growth rate Dietinduced obesity Nutrition Behavior General purpose Additional Available Data Hematology Clinical chemistry Behavioral Studies Surgical Models Diet Induced Models Sensitised Models Surgical Models Diet Induced Models Sensitised Models Additional Stocks of Outbred Rats price per animal ( ) Stock HsdCpb:ORGA HsdCpb:WU HsdOla:WI Hsd:WI Over weeks, add per week P.O.R.,20 P.O.R. 12,00 1,0 2

25 Fischer F/NHsd F/NCrHsd price per animal ( ) Male Female Over 12 weeks, add per week * For our pregnancy policy, refer to page. 1, 1,0 1,0 21,0 2,2 2,0 2, 0,10 2,,,,0 1,00 1,0 1, 1,2 21, 2, 2,0 2,0,0,0 10,0 11,0 122,20 1,00 1,0 F Inbred Rats Albino. F/NHsd; Descended from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. F/NCrHsd; From National Institutes of Health, Bethesda, Maryland; to the National Cancer Institute, Frederick, Maryland in 1; to Harlan Laboratories, in 1. Litter Average:. Haplotype: RT1 lv1 Hydrocephalic resistant Experimental allergic encephalomyelitis Carcinogenicity Oncology Toxicology Aging Ophthalmology Autoimmunity General purpose Survival (%) Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Additional Available Data Hematology Clinical chemistry 2 year growth Surgical Models Diet Induced Models Sensitised Models Aging available for F rats tel + (0) fax + (0) 1 2 [email protected] 2

26 Brown Norway Lewis Inbred Rats BN/RijHsd BN/SsNOlaHsd price per animal ( ) Male Female Over 12 weeks, add per week 1,00 1, 1,0 21, 2,0 2,20 2,0 0,0 2,0,0,0 2,0 2,0 2,1 1,00 1, 1,0 21, 2,0 2,20 2,0 2,0 0,0,0 1,0 2,0 2,1 LEW/Han Hsd LEW/SsNHsd price per animal ( ) Male Female Over 12 weeks, add per week 12,0 1, 1, 1,0 1, 20,0 22,1 2,20 2,0 2, 1, 2, 1,2 1,0 12,0 1, 1,1 1, 22, 2,0 2, 2,,00 112,0 122, 1,2 1,0 * For our pregnancy policy, refer to page. Brown, nonagouti. BN/RijHsd rats were derived from a nucleus colony obtained directly from the TNO Institute, the Netherlands. BN/SsNOlaHsd. In 10 from National Institutes of Health, Bethesda, USA to Olac (now Harlan Laboratories) * For our pregnancy policy, refer to page. Albino. LEW/Han Hsd rats were descended from the Central Institute for Laboratory Animal Breeding (ZfV), Hannover, Germany. In 1 to Harlan through acquisition. LEW/SsNHsd rats were descended from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland USA. Litter average:. Hyperresponsive lungs Allergic respiratory disease Aging Nephrology Surgical Models Sensitised Models Haplotype: RT1 n High incidence of bladder tumors in males Oncology Leukemia Diet Induced Models Litter average:. Haplotype: RT1 l Increased levels of serum thyroxine, insulin, and growth hormone Adjuvantinduced arthritis Transplantation Additional Available Data Clinical chemistry Surgical Models Sensitised Models Docile disposition Inbred recipient for several congenic strains Susceptible to induction of autoimmune disease Experimental allergic encephalomyelitis Diet Induced Models BROWN NORWAY LEWIS Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. 2

27 *Spontaneously Hypertensive Wistar Kyoto SHR/NHsd price per animal ( ),10,20 0,,0,0 0,0,0 10, ,00 12, 1 0,0 1, Over 1 weeks, add per week, * 20, * 21,0 2,0,0 2, WKY/NHsd price per animal ( ) 1, 21, 2, 2,0 2,0 0,0, 10,0 11 1,0 12,0 1,0 1,10 Over 1 weeks, add per week, 10, 12,0 12,20, 1,0 Inbred Rats ** For our pregnancy policy, refer to page. Albino. Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. Litter average:. Haplotype: RT1 k Model for Hypertension and Insulin resistance Additional Available Data To maintain the phenotype of SHR/NHsd rats, Harlan Laboratories routinely screens future breeders utilizing the tail cuff method for acceptable blood pressure levels. On request we can monitor individual rats prior to shipment. * For our pregnancy policy, refer to page. Albino. Derived from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. Litter average:. Haplotype: RT1 k Normotensive control for SHR Model Surgical Models Diet Induced Models Sensitised Models WKY Surgical Models Sensitised Models Diet Induced Models SHR Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. tel + (0) fax + (0) 1 2 [email protected] 2

28 WAG DA Inbred Rats WAG/RijHsd price per animal ( ) Male Female Over 12 weeks, add per week 1,00 1,0 22,10 2,20 2,0 1,,0, 1,10,,0,,0 1,0 1,00 1, 2, 0,00, 1,, 10, 12,0 1,,0 1,0 DA/OlaHsd price per animal ( ) Male Female Over 12 weeks, add per week 1, 1,0 1,20 1,0 1,0 22,1 2,2 2,0 2,0 0,,1 2,,0 1,0 1, 1, 1, 21,10 2,0 2,,00 2,,,,0,0 1,0 * For our pregnancy policy, refer to page. Albino. WAG/RijHsd rats were obtained from the Radiobiological Institute TNO, in Rijswijk, the Netherlands. Through acquisition to Harlan Laboratories in 1. * For our pregnancy policy, refer to page. Agouti. From A.R.C. Cambridge, United Kingdom; to Olac, United Kingdom, in 1; to Harlan Laboratories, in 12. Surgical Models Sensitised Models Diet Induced Models WAG Litter Average:.0 Haplotype: RT1 av1 Females have a defective bile acid transport Experimental allergic encephalomyelitis Induced rheumatoid arthritis Oncology Cardiovascular Transplantation Surgical Models Diet Induced Models Sensitised Models DA Additional Strains of Inbred Rats price per animal ( ) Strain ACI/SegHsd BUF/SimRijHsd LE/CpbHsd LOU/MWslHsd PVG/OlaHsd SR/JrHsd SS/JrHsd WF/NHsd Over weeks, add per week,0,00 2,0 2,1 20,,,,,2 2 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet.

29 Aged Rats Sprague Dawley Hsd:Sprague Dawley SD Age (months) Base price ( ) Add per month ( ) 12,20 12, starting th month 121 1,1 1,00 starting 1th month 1+ 2,1 2,1 starting 1th month Albino. Originated by the SpragueDawley Company, Madison, Wisconsin, in 12 through a series of crosses begun with a singlehooded male and six albino females of unknown origin. Current Harlan colonies are direct descendants of this original colony. Fischer F/NHsd Age (months) Base price ( ) Add per month ( ) 12 0, 12, starting th month 121 1,0 1,00 starting 1th month 1+ 2,0 2,1 starting 1th month Albino. Descended from a nucleus colony obtained from the National Institutes of Health, Bethesda, Maryland. Wistar Han RccHan :WIST Age (months) Base price ( ) Add per month ( ) 12 0,0 12, starting th month 121 1, 1,00 starting 1th month 1+ 2, 2,1 starting 1th month Albino. Derived from animals from RCCBRL (Biological Research Laboratories Limited), Basel, Switzerland, in 1. To Harlan Laboratories through acquisition in 200. Cohorts of the listed male rat models are reserved monthly for agedanimal inventory. Pricing of aged animals from the aging inventory is available upon request. If the requested aged animals are not available from our aging inventory, or require three or more months of maintenance prior to shipment, Harlan will age a reserved cohort of animals to accommodate client research requirements and account for anticipated loss from natural attrition. Pricing for clientreserved aging cohorts will be developed based on the requirements of the project. Prior to initialization of an aging project, Harlan will confirm client expectations, the project work scope, and animal pricing with a written agreement of understanding. Memory Osteoarthritis Neoplasia Immune response Longevity Vision and hearing Motor skills Renal degeneration Ageassociated pathology Metabolism Neurobiology Cardiovascular Reproductive senescence Aged and Hybrid Rats FBNF1 FBNF1/Hsd Age (months) Base price ( ) Add per month ( ) ,00 1, starting th month 121 2, 2,0 starting 1th month 1+ 0,,10 starting 1th month Dark brown, nonagouti. Offspring of a cross between the F/NHsd inbred female and the BN/RijHsd inbred male. Common AgeAssociated Conditions Include: Hair loss Loss of motor skills and sensory perception Presence of spontaneous tumors Reduced immunologic and physiologic function Loss of vision, e.g. retinal degeneration, development of cataracts Surgical Models Diet Induced Models Sensitised Models Hybrid Rats Strain FBNF1/Hsd* Over weeks, add per week price per animal ( ),0,1 When planning for your aged animal requirements, please consider the need to reserve extra animals on your order to replace any losses due to natural causes. * Aging models of this strain are available. Please refer to page 2 for full details. This is a brief selection of hybrid rats; any combination can be bred on demand. For the same reason, any existing hybrid combination can be discontinued at any time without prior notice. tel + (0) fax + (0) 1 2 [email protected] 2

30 *Athymic Nude *Zucker Mutant and Transgenic Rats Hsd:RHFoxn1 rnu price per animal ( ) rnu/rnu rnu/+ Over weeks, add per week 0,, 1,0,0 102,0 10,0 11,,0,0,0 2,,,0, 2,2, P.O.R. P.O.R. P.O.R. Hooded (pigmented). In 1 from Central Institute for Laboratory Animal Breeding (ZfV), Hannover, Germany, to Harlan through acquisition. * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. HsdOla:ZUCKERLepr fa price per animal ( ) fa/fa lean** Over weeks, add per week 111,0 11,0 11,2 121, 12,,0,, 2,0,,20,0 P.O.R. P.O.R. P.O.R. Black. In 10 from Wellcome Laboratories, Dartford to Olac (now Harlan Laboratories). Additional related genotypes: HsdOla:ZUCKERLepr fa /Lepr +, HsdOla:ZUCKERLepr + * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. ** Genetic testing is required to determine Lepr fa /Lepr + or Lepr + /Lepr + genotype. See page 1 for genotyping services available from Harlan Laboratories. The rnu allele on chromosome 10 is an autosomal recessive mutation associated with hairlessness and thymic aplasia The thymusdependent lymph node areas are depleted of lymphocytes (Tcells) Phenotypically hairless (sparse hair growth possible) Rudimentary thymic tissue Increased Natural Killer (NK) cell population Foxn1 rnu /Foxn1 + heterozygotes do not show partial expression of rnu phenotype Produced in flexiblefilm isolators. Monitored for Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter spp, Pneumocystis carinii, and other commensal opportunistic organisms Immunology Xenograft and allograft transplantation Additional Available Data Proven models with extensive reference (see page 2). Surgical Models Diet Induced Models Sensitised Models Visit us at for our full portfolio on oncology products and services or ask for our oncology brochure fa is an autosomal recessive mutation on chromosome Exhibit obesity at to weeks of age Adipocyte hypertrophy and hyperplasia Lepr fa /Lepr + heterozygotes do not show partial expression of fa phenotype Genetic obesity Diabetes, type II Additional Available Data Hematology Clinical chemistry 12 week growth Surgical Models Sensitised Models Additional Stocks of Mutant and Transgenic Rats Stock Hsd:HIV1 (F) Over weeks, add per week Animals have not been selectively bred to induce hyperglycemia Insulinresistant Hyperphagia Muscle atrophy Hyperlipemic Hypercholesterolemia Hyperinsulinemia price per animal ( ) 1, 11,1 * The breeding supply and use of this strain is regulated under the Animals (Scientific Procedures) Act, 1; supply to order is dependent on prior authority having been obtained from the Secretary of State through the Home Office Inspectorate. 0

31 Golden Syrian Hamsters Cotton Rat HsdHan :AURA price per animal ( ) 2, 0 2,0 0 0, 0 2, ,0 120+,0 Untimed pregnant female,0 Time mated female,,00 2,20 1,0 Golden brown and white. Colony established in 1 with stock originating from Zentralinstitut fur Versuchstiere, Hannover, Germany. The source for the Hannover colony was the SpragueDawley Company in 1. Hsd:Cotton Rat price per animal ( ),0, 2,,0, 2,0,0 Over weeks, add per week,0 Color combination varies: gray, brown, black. Sigmondon hispidus (Cotton Rat) is a New World rodent that was developed by the National Institutes of Health, Bethesda, Maryland, and Virion Systems, Inc. In 1, Harlan obtained a breeding nucleus from Virion Systems, Inc. Hamsters and Cotton Rats Litter average:.0 Excellent reproductive performance Syrian Hamster Embryo (SHE) Cell Transformation Assay Toxicology Carcinogenesis Behavior Hypercholesterolemia Infectious disease (Clostridium difficile) Hibernation Additional Available Data Hematology Clinical chemistry Litter average:. Susceptible to a wide range of human infectious disease agents Adenoviral vectorbased gene therapy Infectious disease pathogenesis Respiratory Syncytial Virus Herpes Simplex Parainfluenza Type Polio Measles Monkeypox Surgical Models Diet Induced Models Sensitised Models Surgical Models Diet Induced Models Sensitised Models AURA Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 201S diet. tel +1 (0) 00 fax +1 (0) [email protected] 1

32 Dunkin Hartley NZW Guinea Pigs and Rabbits HsdDhl:DH HsdPoc:DH price per animal ( ) Over 00, per 0 gr. extra Untimed pregnant female Time mated female,1 1,0, 1,0,,0 0,00,0,20,10 200,0 21, 2, 10,0 2, Albino. Dunkin Hartley strain originally from Agriculture Research Centre at Comptom in 1 HsdIf:NZW price per animal ( ) Age(weeks) Approx. weight (kg) Up to , , , , , , , , , , , Over 20 weeks, add per week Untimed pregnant female Time mated female LH Injection 1, 2,0,0,00, 11, 10,0 Compact animal with excellent breeding performance, used in multiple research disciplines Surgical Models Diet Induced Models Sensitised Models Albino. Derived from three commercial UK sources of New Zealand White rabbits. Through acquisition of Interfauna UK to Harlan in 1. Litter Average:. Production software for tracing individual rabbit lineage Individual identification via tattoo, or microchip on request Toxicology Teratology Dermatology Opthalmology Biomedical Research Osteology Artherosclerosis Antibody Production Cardiovascular Renal Additional Available Data Hematology Diet Induced Models Surgical Models Sensitised Models DUNKIN HARTLEY NZW 2 Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 20 diet. Growth chart data should be used as a guideline only. Animals were bred and maintained on Teklad Global 20 diet.

33 Beagles APD Beagles HsdRcc:DOBE HsdIf:DOBE price per animal ( ) 112,0 0 11, , , , , , , , 22 10,0 22 1, ,1 20 1, , 12,00 10,0 12,0 0 2,0 Over 0 weeks, add per week,0 Over 2 weeks, add per week 112,0 HsdCpb:DOBE(APD) price per animal ( ) Bred and maintained under partnership. Availability and pricing on request Antibody Profile Defined (APD) Beagles Free of antibody to Canine Distemper Virus (CDV), Canine Adenovirus (CAV), Canine Parvovirus (CPV), Canine Coronavirus (CCV), Canine Parainfluenza Virus (CPI), Canine Herpes Virus (CHV), Leptospira canicola, Leptospira icterohemorrhagiae, Rabies Virus. Unvaccinated and barrierreared to assure freedom from diseases or humoral antibodies affecting disease susceptibility and progression Dogs Socialization program begins at an early age. Special handlers socialize the beagles daily. This interaction makes Harlan beagles more manageable and easier to work with in a research environment Purpose bred, socialized, and vaccinated for conventional biomedical research Colony Management Housing pens constructed to assure optimal safety, sanitation, socialization, and observation Individual breeder records are maintained to ensure pedigree, mating of unrelated animals, and for reference Additional Available Data Complete blood counts Serum chemistry Growth curve Postponement Policy Dogs All orders which are postponed will incur a administrative charge as detailed: 1. First postponement to incur an admin charge of 0 per dog. 2. Second postponement to incur an admin charge of 100 per dog.. Third postponement would incur a full cancellation charge and the order cancelled automatically. Maximum duration a postponed order is allowed to move is weeks. Surgical Models Diet Induced Models tel + (0) fax + (0) 1 2 [email protected]

34 Biological Products and Services Biological Products Introduction A major advantage of Harlan Laboratories biological products is that they are collected from our own laboratory animals. Harlan has a worldwide reputation as a producer of the highest quality laboratory animals of which specific strains of species are also available. The animals are raised under closely defined conditions to ensure consistent high quality products. Rodents and rabbits are raised in strict barrier conditions, which are monitored on a regular basis for pathogens. Dogs, cats, marmosets and other primate species are maintained as closed genetically controlled colonies and their health status is monitored regularly. All animals are fed a controlled naturalingredient diet. Standard diets, close attention to production, and good health care minimise lottolot variation. The availability of a large supply of commercially bred stock allows us to be more responsive to customer requirements for quality and quantity. In addition to these commercially bred animal species, we have further access to a large range of farm animals for supply of different blood products. Blood Products All whole blood products are aseptically collected from healthy, adventitious virus free Harlan barrierreared animals (according to FELASA Recommendations) or genetically controlled colonies. Blood is collected fresh for each customer order and can be checked for haemolysis before being despatched on the day of collection. Upon ordering, please specify the type of anticoagulant required. Blood collected into Alsevers is adjusted to a standard packed cell volume to ensure product consistency. Sterile filtered serum Serum Services Because we use our own serum for inhouse procedures we can provide expert help in selecting the best serum for the project at the best price. Our Customer Services Department can help you select the most appropriate batches for your cells by comparing your needs with our database. Contact us for additional information on [email protected]. Heat Inactivation Harlan can heat inactivate any serum on request. Serum is heat inactivated under thermostatically controlled conditions at C and maintained at this temperature for 0 minutes with constant mixing. This process is used to destroy complement and to ensure that cells will not be lysed during antibody binding. A Certificate of Heat Inactivation is supplied with each order. Raw Serum All serum provided by Harlan is raw, nonsterile, unfiltered material from healthy, adventitious virus free animals (according to FELASA Recommendations) raised in strict barrier conditions or genetically controlled colonies. All serum is quality control tested for Haemoglobin as well as physical appearance to ensure that they meet standard specifications. A Certificate of Analysis is provided with each batch of serum dispatched. For information and costs of sterile filtration, heat inactivation, gamma irradiation or bulk quotations please contact our Customer Services Department. Serum can be provided in different standard vial sizes; pooled products are readily available from stock. Product from specific stocks or strains bred at specific age and sex are collected on request and require therefore a longer lead time. Plasma Harlan s plasma is from an extensive range of healthy, adventitious virus free animals (based on the FELASA Recommendations 2002, Nicklas et al). These animals are raised under strict barrier conditions or genetically controlled colonies. All plasma is supplied as raw, nonsterile, unfiltered material in a choice of anticoagulants. All plasma is quality control tested for Haemoglobin as well as physical appearance to ensure that they meet standard specifications. A Certificate of Analysis is provided with each batch of plasma despatched. Upon ordering, please specify the type of anticoagulant required. Most commonly used are: EDTA, Lithium Heparine, Sodium Heparine and Citrate. Plasma can be provided in different standard vial sizes; pooled products are readily available from stock. Product from specific stocks or strains bred at specific age and sex are collected on request and require therefore a longer lead time. Please discuss your specifications with us, so we deliver the right product to you, meeting your research needs. Complement Guinea Pig Complement Harlan s Guinea Pig complement is collected from pooled sera of healthy animals that have been raised under closely defined conditions, therefore minimising lottolot variation. The technique used to process the sera ensures high complement activity and is in line with the recommendations of the European Health Committee. The complement is screened by a standard haemolytic titration assay against the British Reference Reagent. Endogenous nonspecific cytotoxicity in the absence of antibody has been quantified. Because of the variation in complement fixation tests and assays, Harlan supplies free of charge samples for testing against reserved batches. Rabbit Complement All rabbit complement is collected from healthy rabbits and the technique used to process the sera ensures high complement activity. The complement is tested by appropriate assays to ensure high activity and low cytotoxicity. Baby Rabbit Complement Normal rabbit serum is collected and pooled from young rabbits 212 days old. The complement is prepared in line with standard lymphocytotoxicity techniques. Rabbit Complement for use with Mouse Lymphocytes Rabbit serum is normally cytotoxic to mouse lymphocytes, particularly thymocytes. The cytotoxicity in this complement has been significantly reduced by absorption with mouse tissues and agarose. Tissues, Organs and Glands Due to the resources of the Harlan group worldwide, Harlan is able to provide an extensive range of tissues, organs and glands from many animal species. Controlled breeding under strict barrier conditions or genetically controlled colonies ensures the health status of the animals and maintains products of the highest quality. The range of organs include, but is not limited to: brain, eyes, heart, kidney, liver, lungs, ovaries, pancreas, prostate, spleen, stomach and testicles.

35 All tissues, organs and glands are collected, flash frozen in liquid nitrogen and are normally shipped on dry ice. Products can be provided fresh or in preservative for specific customer requirements. We are also pleased to quote for bulk shipments. Specific strains and animals of specific age and sex can be obtained on request. Antibody Services Custom Antibody Services Harlan Laboratories endeavours to supply high quality antibody produced promptly and efficiently. We have expanded our existing range and included a number of new services that allow us to offer further cost effective solutions to your antibody needs. Our customer service and technical team will discuss your individual requirements to ensure we supply the most appropriate services for your project. Advice and development of individual projects to fullscale collaborations can easily be catered to. Our quality is measured by the performance of your antibody before, during and after your production is completed. Services Include: Polyclonal Antibody Production Monoclonal Antibody Production Purification Conjugation ELISA Testing Cell Banking Harlan continues to look for more ways to serve the research community worldwide. Please contact us to set up a schedule that will meet your requirements. Polyclonal Antibody Services Polyclonal antibody production is performed inhouse by Harlan at its expanded facilities in Europe using pathogen free barrier reared rodents and rabbits direct from Harlan. Barrier raised animals provide greater reproducibility and often produce higher titres with lower background signals. Our facilities are regulated and controlled under strict guidelines ensuring a high standard of animal care and documentation by our dedicated staff. Standard procedures are in place for all procedures including immunisation, blood sampling and serum preparation. All procedures are fully documented allowing complete traceability. Protocols Harlan has established protocols for polyclonal production for different species using either standard or premier packages Alternatively, we can use protocols modified to our customers requirements. Tell us the number of immunisations and bleeds you require, and we will incorporate this into a format for your approval. A protocol may be extended beyond its original finish date. We ask the enduser to confirm by fax/ hrs in advance of termination. Animals Harlan can currently perform polyclonal antibody production in a variety of different species including: rabbit, chicken, goat, sheep, guinea pig, rat, mouse, dog and pig. If you require production in any animals not listed, pleased contact us. Antigens Antigens can be supplied either in solution or lyophilised, conjugated to a carrier protein, or we can conjugate it for you. Look at our website for details on our antigen conjugation services. Immunisations Immunisations are performed routinely by subcutaneous injection. Rodents can be immunised with up to 0. 1ml at each of 2 sites giving a total volume per immunisation of 0.2ml. Other animals may be immunised with up to 0.2ml at each of sites giving a total volume of 1.0ml per immunisation. Adjuvants Polypeptides smaller than 10 kda and nonprotein antigens usually need to be conjugated to a carrier protein to become good immunogens. Additionally these, as well as other protein antigens, need to be administered with an adjuvant to ensure a high quality/quantity response. This is especially true if low levels of antigen are to be administered. There are a number of adjuvants that are available for use in polyclonal antibody production. Complete Freund s adjuvant continues to be the most commonly used despite its potential hazards. In order to eliminate or reduce discomfort, national guidelines may require adequate justification for the use of Complete Freund s. Monoclonal Antibody Production In vitro Harlan has years of experience in producing monoclonal antibodies. Working together with Harlan Bioproducts for Science in the U.S.A., specialists in ascites production and hybridoma development, Harlan can supply a wide range of services. We understand each antibody can react differently and each project has specific needs. Because of this, we have developed a range of immunological services to support the small and largescale needs of our customers. We will work closely with you to ensure you get the package that best suits your requirements. Our team will consult with you throughout the project offering advice and technical expertise. Biological Products and Services In order to satisfy regulations, a brief justification of the project to be undertaken is required before the protocol can commence. All antigens submitted for polyclonal antibody production must be accompanied by a statement (such as e.g. COSHH) detailing all risks associated with the handling of the antigen. tel + (0) fax + (0) 1 2 [email protected] [email protected]

36 Biological Products and Services In Vitro Monoclonal Antibody Production Monoclonal antibodies can be manufactured in several different systems. Since different cell lines differ significantly in levels of antibody production, we can evaluate your hybridoma before starting the procedure. Large Scale Production Programme A If you are looking for antibody production over 10 grams the optimisation of your cell line is vital to ensure that you obtain the maximum antibody from a given cell line. In our hollow fibre system, we will perform a 0 day production run. Following your evaluation of the resulting antibody, we will provide a quotation to produce the additional amount of antibody required. Harlan can produce 0mg to 10g of antibody in vitro in a 0day production run. Small Scale Production Programme B If you are looking for smaller amounts of antibody, we offer a continuous hollow fibre protocol that gives you complete control of the length and cost of your project. You pay a standard setup and weekly maintenance fee and are then charged a standard rate for weekly harvests for as long as you require. Antibody Purification Services Harlan can purify your monoclonal and polyclonal antibodies using a wide a variety of purification methods, based on a minimum starting volume of 10 ml. The correct choice of purification method will depend on a number of variables. These include the use for which the antibodies are intended, the species in which it was raised, its class and subclass, and the source (e.g. supernatant, serum, or ascites). We are happy to discuss your purification options and develop the purification procedure that provides the best balance between yield, purity, and cost. A full profile with analysis by SDS page and production records is supplied with each purification. Purification methods available include: Ammonium Sulphate Precipitation Protein A Affinity Chromatography Protein G Affinity Chromatography Ion Exchange Chromatography (anion and cation) Ig Affinity Antigen Affinity Size Exclusion Chromatography Antibody Conjugation Services Harlan offers antibody and antigen conjugation services. Choosing the best conjugate for your application is not always easy. We can help you decide on the most suitable conjugate for your applications. Biotin Biotin is the conjugate of choice if the antibody is going to be used in a variety of applications. Biotin is a small molecule that has little effect on an antibody s immunoreactivity. Its small size makes biotin an excellent tag for your antibody in most techniques. Biotin binds tightly to avidin or streptavidin, which are available enzyme conjugated, making your biotinylated antibody useful in most immunological procedures. The disadvantage of a biotinylated antibody over an enzyme or fluorescent conjugated antibody is that there is an additional step involved in your assay. HRP and Alkaline Phosphatase Enzyme conjugates give a highly selective and sensitive immunoreagent. By directly labelling your primary antibody you eliminate steps and washes. Horseradish Peroxidase is a stable enzyme suitable for ELISA, Western Blot and Immunocytochemistry. HRP has low endogenous activity and a high turnover rate, producing its coloured end product in a short time period. Alkaline Phosphatase is often used when high background is experienced with HRP interacting with endogenous peroxidases. Alkaline Phosphatase allows linear reaction rates improving sensitivity by reacting over longer time periods. Fluorescent Markers Fluorescent probes are used in multiple probe assays, immunofluorescence microscopy and flow cytometry. A minimum quantity of 2mgs of antibody is required for all conjugations. Biosafety Testing Harlan now offers a range of biosafety tests to their customers. Sterility Testing This procedure is performed to determine if the test material is free from bacterial and fungal contamination. Endotoxin This assay is performed to determine if bacterial endotoxins are present in the test material. Mycoplasma This assay is performed to detect mycoplasma contamination in biological material. In the event a test material is positive for mycoplasma contamination Harlan can arrange mycoplasma species identification testing. Cell Banking We offer a cell banking facility to our customers. We can store any size of bank from 10 to 200 vials. No setup fee. Temperature is maintained below 1 C and is constantly monitored and logged. Any deviations in temperature will be reported to the customer. Access to the bank is restricted and recorded. Regular viability checks are made using at least cell lines. An annual certificate is supplied confirming the number of ampoules stored, and results of viability tests. Customer cell stocks must be tested prior to storage to check for freedom from mycoplasma, viruses, bacteria and fungi. This can be done by Harlan or documentary evidence should be supplied before cell stocks are shipped.

37 Contract Research Services Harlan Laboratories is a global market leader within Contract Research Organizations with over 2 years of experience in testing, registration, and consulting services. Formerly known as RCC, SafePharm, and Harlan Biotech, we have come together under a single banner worldwide, with one vision, one set of values and a companywide passion for scientific excellence. Discovery Services We are focused on fast turnaround, both in study initiation and reporting. Our unique combination of Research Models, Diets, and Services will help you succeed in today s competitive market. Pharmacokinetic Screening Lead Optimization/Early Toxicology Screening AAALAC Accredited USDA Licensed for Research Lead Optimization/Early Toxicology Screening Our Lead Optimization services allow our partners to determine the best path for their molecules, to ensure a successful candidate for future GLP studies. Customized Study Designs Variety of rodent and nonrodent species available Variety of routes of administration Clinical Pathology/Histopathology Dietinduced disease models Surgical Models PK/TK Drug Metabolism and Pharmacokinetics Surgical Models Bioavailability Tissue Distribution Single Dose Repeat Dose Cassette Designs Formulation Optimization Bioanalytical Services Toxicology Services General Toxicology Safety Pharmacology Reproductive Toxicology Neurotoxicity Testing Carcinogenicity Studies Inhalation Toxicology Genotoxicity and Cell Biology Mechanistic Studies Medical Device Testing Special Techniques in Toxicology Pathology and Histopathology Analytical and Bioanalytical Services Regulatory Affairs, Consulting, Program Management Animal Facility Management and Consulting Archiving Quality Assurance Regulatory Affairs Strategic Partnership with Industry Species Available Rodent, rabbit, canine, minipig, NHP Other species/specific strains upon request Our Contract Research Services operating group provides laboratory research services worldwide, tailored to your specific needs, to ensure that your research makes a difference in improving people s lives. Contract Research Services Other Discovery Services Include Shortterm Infusion Studies Special Diet and Feeding Studies Metabolic Studies Xenograft Studies Vaccine Studies Rodent Tissue, Gland and Organ Collection Services Visit our website for our full programme or contact us at [email protected] for detailed questions. tel + (0) fax + (0) 1 2 [email protected]

38 Innovation and consistency Teklad Diets & Bedding Diet should reduce rather than introduce variation Teklad Global Diets are the world s leading laboratory animal diets. Innovatively designed for biomedical research It s not enough to meet basic nutritional criteria; diets should reduce rather than introduce variation. Teklad Global Diets are an integrated range of natural ingredient diets for specific life stages, containing levels of protein, energy, vitamins, and minerals that more closely align with nutritional requirements. The Global Rodent Diets are vegetarian and reduce or exclude ingredients that contain components (such as phytoestrogens and nitrosamines) which can affect the consistency of research results. What is fixed formulation? Fixed formula diets contain the same ingredients, in the exact same quantities, in every batch of diet produced. Other manufacturers may use variable formula diets in which both ingredients and inclusion rates are changed to an extent unknown by the investigator. Why fixed formulation? Natural ingredients contain a variety of nutritive and nonnutritive components. Examples of the latter include phytoestrogens, phytosterols, and antioxidants. Both nutrients and nonnutrients can have significant effects on research. Because we do not change the formula from batch to batch, the variation in nutrient and nonnutrient levels is minimized, meaning consistent results for you. What makes Teklad Global Diets better? FEATURE BENEFIT Fixed Formulation Same exact formula every time leads to reliable research results Quality control program includes single source suppliers, stringent ingredient procurement, and testing prior to acceptance into mill to ensure consistency in finished product Quality, Production & Packaging ISO 001:2000 or GMP Certified facilities Certified Diet options readily available Global supply chain with redundant production capabilities both in Europe and the U.S. Documented manufacturing checks and product testing throughout the entire process verifies consistency Standardized item codes, colorcoding, and icons for ease of package identification Storage, Handling & Delivery Manufacturerdirect control Climatecontrolled warehouses maintain nutritional integrity Validated biosecurity and rigorous vermin control programs at all sites Global availability allows for convenient and costeffective worldwide harmonization Technical & Client Support Nutritionists dedicated to answering your questions Customer service centers worldwide Local sales support Phytoestrogens Reducing research variables Teklad Global Rodent Diets reduce or eliminate soybean meal and exclude alfalfa meal, thereby reducing phytoestrogens. Soybean and alfalfa meal are the major sources of phytoestrogens in laboratory rodent diets (mainly daidzein & genistein; and coumestrol, respectively). These naturally occurring compounds can potentially affect research results through interaction with endogenous estrogens and via other mechanisms. Phytoestrogens may substantially diminish the effectiveness of animal models of disease and adversely affect the consistency of experimental results. Research areas affected by phytoestrogens Reproductive & endocrine disruptor studies Cancer studies Breast, prostate, colorectal, lung Cardiovascular disorders Thrombosis, atherosclerosis Lipid and cholesterol studies Diabetes & other endocrine studies Insulin, vasopressin, thyroid hormones Bone metabolism studies Central nervous system studies Behavior, memory, learning, neural degeneration Immunology Gene expression studies

39 VARIATION IN PUBLISHED ISOFL AVONE (DAIDZEIN AND GENISTEIN) CONCENTRATIONS BETWEEN DIETS, AND BETWEEN BATCHES OF THE SAME DIET Isoflavone Concentration (mg/kg) Harlan Teklad Global Diets Traditional US diets Traditional European and Japanese Diets For experimental endpoints sensitive to isoflavones, this batch to batch variation can lead to inconsistent experimental results. This plot shows published literature values for isoflavone levels in traditional diets from NA (red), Europe and Japan (black), together with independent laboratory values from the Global Rodent Diets (green). Each symbol is one value and symbols within a column denote multiple values for that diet. The Teklad Global Rodent Diets are 1) 201, 2) 201, ) 201, ) 201X, ) 2020X. 201 contains a reduced amount of soybean meal compared to many traditional rodent diets, while the other Global Rodent Diets contain none. All Teklad Diets are fixed formulas. Teklad Diets & Bedding Manufacturer/Diet Custom Research Diets, Medicated Diets & Bedding Custom research diets Custom diets are an important research tool. Most are developed for a specific purpose and benefit from your input and our expertise. With over 20,000 formulas in our database attained over 0 years, Harlan nutritionists have vast experience to draw upon. We are committed to developing and maintaining longterm customer relationships. Common classes of custom diets include: Highfat (00% kcal from fat) High Carbohydrate (fructose, sucrose) Atherogenic (cholesterol, fat, cholate) Vitamin & mineral adjusted Amino acid defined Doxycycline containing diets Addition of customer supplied ingredients/compound Teklad Custom Diets are shipped throughout the world. Medicated diets As some compounds are best administered orally, several medicated diets are available from stock. Use as directed by a veterinarian. Bedding The importance of bedding is often overlooked, yet your animals are in close contact with bedding on a continuous basis. That s why we ve carefully reviewed most available bedding options, and now offer a defined full product line including corn cob, wood, and paper products. Most of our beddings have been tested in our own animal production barrier. Because of the importance of bedding quality, we now produce several of these options in our own bedding plant which is dedicated to production for the research community. Certified and irradiated options are available for most items. Contact us for information or samples of the products available in your region. Enrichment products We offer several unique environmental enrichment items, featuring our 122 Irradiated Enrich Mix for nonhuman primates. Cottonbased isopads and isoblox enrichment and nesting materials for rodents combine enrichment with superior product sanitation and safety (no long strands or fibers). Based on the nature of the products, some cannot be exported overseas without proper import licenses in the specific country of destination. T F2 201 Rodent Diet with 10 ppm Fenbendazole Contact us for technical support at [email protected] Other medicated diets are available in smallscale or largescale production. Contact us for more details. tel + (0) fax + (0) 1 2 [email protected]

40 Packing Guidelines The following grids are guidelines for you to use to determine the number of shipping containers required to ship your laboratory animals. Please keep in mind that certain types of animals may require special packing guidelines other than those shown below. Packing Guidelines Mice Small Large Hamsters Double insulated Rats Small Large Guinea Pigs Rabbits Up to Number per box 2 Weight (kg) Up to 1.0 Over 1.0 Number per box 2 1 Isolator Reared Mice Mutant Mice Age (wk) 10 Large This box is for nude, obese and diabetic mice Double insulated 12 The animals are shipped in IATA approved filtered boxes. The filtered boxes are supplied with agar and/or diet to ensure that the animals arrive in excellent condition. All of our animals are shipped in climatized vehicles according to a weekly route. Mutant Rats Age (wk) 10 >10 This box is for nude rats Double insulated 2 0

41 Microbiological and Genetic Monitoring Microbiological Monitoring The Harlan comprehensive monitoring programme includes monthly evaluations of barrierproduced rodents and monthly to quarterly evaluations of flexiblefilm isolator produced rodents. Updated Health Reports are available at Microbiological Evaluation Mouse Serology Mouse Parvovirus (MPV) Mouse Minute Virus (MMV) Sendai Pneumonia Virus of Mice (PVM) Mouse Hepatitis Virus (MHV) Mouse Norovirus (MNV) Theiler s Mouse Encephalomyelitis (TMEV) Reovirus (Reo) Mycoplasma pulmonis Mouse Rotavirus (EDIM) Lymphocytic Choriomeningitis (LCM) Mouse Adenovirus 1+ 2 Ectromelia Polyoma Mouse K Virus Lactic DehydrogenaseElevating Virus (LDEV) Mouse Cytomegalovirus (MCMV) Hantavirus Encephalitozoon cuniculi Cilia Associated Respiratory Bacillus (CARB) Clostridium piliforme Rat Serology Sendai Pneumonia Virus of Mice (PVM) Rat Coronavirus (SDA/RCV) Kilham Rat Virus (KRV) Toolan s H1 (H1) Reovirus (Reo) Mycoplasma pulmonis Rat Minute Virus (RMV) Rat Parvovirus (RPV) Rat Respiratory Virus (RRV) Theiler s Mouse Encephalomyelitis (TMEV) Lymphocytic Choriomeningitis (LCM) Mouse Adenovirus 1+ 2 Hantavirus Encephalitozoon cuniculi Cilia Associated Respiratory Bacillus (CARB) Rotavirus Clostridium piliforme Guinea pig Serology Guinea pig Adenovirus (GpAd) Sendai Guinea pig Cytomegalovirus(GPCMV) Lymphocytic Choriomeningitis (LCM) Reovirus (Reo) Encephalitozoon cuniculi Clostridium piliforme Chlamydia psittaci Hamster Serology Lymphocytic choriomeningitis (LCM) Sendai Clostridium piliforme Encephalitozoon cuniculi Rabbit Serology Rabbit Haemorrhagic Disease Virus (RHDV) Rabbit Rotavirus Myxomatosis Treponema cuniculi Clostridium piliforme Encephalitozoon cuniculi PCR Helicobacter spp (only mice, rats, hamsters) Corynebacterium bovis (only nude mice) Pneumocystis spp (only immunodeficient animals) Microscopic Evaluations Ectoparasites Endoparasites Pathological lesions Bacteriology Culltures from the nasopharynx and caecum are routinely cultured for the presence of the following microorganisms: Bordetella bronchiseptica Citrobacter rodentium Corynebacterium kutscheri Klebsiella oxytoca Klebsiella pneumonia Pasteurella spp Proteus spp Pseudomonas aeruginosa Salmonella spp Staphylococcus aureus B Haemolytic streptococci (not D) Streptococcus pneumoniae Streptobacillus moniliformis Yersinia Pseudotuberculosis Dermatophytes Organisms that are cultured using the media and methods used to culture the organisms above are identified to genus level. These data are available on request. The lists of bacteria included in routine health monitoring reports vary according to species and immune status of the animals, and are based on the FELASA (2002) health monitoring recommendations. Not all the bacteria listed above are included in all routine reports. Complete lists of cultured bacteria (isolates) are available on request. Current microbiological monitoring reports and cumulative summaries are provided upon delivery of our animals or can be reviewed on our website. Reports are also available on request for each animal shipment. Significant changes in health status are promptly reported to clients by phone, fax and . Genetic Monitoring Inbred strains at each production location are tested using a custom panel of Single Nucleotide Polymorphism (SNP) markers. Tests are conducted twice each year on foundation, colonies of each strain of rats and mice. Harlan s Genetic Monitoring Programme Evaluates Physical characteristics Reproductive indices SNP ( markers) Microbiological and Genetic Monitoring Harlan Laboratories maintains a range of mouse stocks and strains, free of opportunistic bacteria to include; Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus aureus and Proteus spp. Contact your Customer Service Department for additional information. tel +1 (0) 00 fax +1 (0) [email protected] 1

42 Surgical Services Surgical Services Harlan Laboratories Europe offers a wide range of surgical services to assist customers with (micro) surgery for rodents and dogs. In our surgical suites we operate on standard and custom surgically modified animals with a focus on animal welfare. Besides the highest standard of surgical prepared animals, we offer customers surgical training courses to master basic and advanced surgical techniques. On demand, we offer special designed Continuing Education Training programmes with specialists in the field including technicians and scientists. Replacement, reduction and refinement (the R s) play an important role in modern biomedical research. Harlan Laboratories surgical training courses and surgically modified animals contribute to the R s principle: good welfare is good science. Customers receive expert advice on surgical techniques and perioperative care in different research areas. Our state of the art surgical suites and skilled surgical team enable us to perform surgery at high speed while minimizing tissue trauma under aseptic conditions. The surgery area is located next to the animal breeding barriers which enables us to have an efficient supply of animal models while maintaining a minimum risk of contamination. Sentinel animals are used to monitor the microbiological status of the surgical prepared animals in order to keep SPF status during and after surgery. Furthermore, the surgery area is divided into preparation, surgery and recovery rooms in order to comply with strict aseptic working methods. All pre and post operative care is undertaken in filtertop cages and or scantainers. Surgical training Surgical training is performed in a dedicated training room with eight surgery tables. Microscopes are equipped with additional oculars to enable our surgical team to see the participants surgical field and give assistance. The surgical field of a demo microscope is displayed on a wide screen monitor to train specific parts of a surgical technique. We offer the following courses: Introduction course; basic principles of (micro)surgery Advanced course; advanced techniques e.g. bile duct catheterization Telemetry course; advanced techniques for implanting telemetry devices Dedicated course; on demand courses e.g. automated blood sampling Dedicated course; on demand courses on site Visit us at for program details and dates Animals will be operated on according to the principles of Good Surgical Practice, which include: Aseptic working method Minimal surgical trauma Perioperative care; also on request Short anaesthesia and analgesia if necessary Detailed reporting; official animal diary Detailed instructions; e.g. work instructions Surgical modified animals Ectomies Insertion of (non) vascular catheters Softtissue procedures Neurological procedures Implantation of radiotelemetry transmitters Implantation of other devices Connection of harnesses, buttons and jackets The Harlan Advantage Strong focus on animal welfare Custom made training programmes, including large animals Full health monitoring in surgical room Good welfare is good science Saves you resources and time Surgical procedures available from Harlan Laboratories UK Ltd. Soft Tissue Procedures Rat Mouse Guinea Pig > 0 (g) > 20 (g) Adrenalectomy Orchydectomy Hysterectomy.00 Ovariectomy Thymectomy Vasectomy Vascular Catheters Rat Mouse Guinea Pig > 10 (g) > 20 (g) Carotid Artery, Common Femoral Artery 1.00 Femoral Vein Jugular Vein (neck attachment).00 Jugular Vein (head attachment) Standard vascular catheter is made of polyurethane with a neck button. Silicone, polyethylene, tapered polyurethane and heparincoated (Instech Solomon CBAS ) catheters available upon request. Price does not include cost of these special catheters. 2

43 Terms and Conditions Our general Harlan Terms and Conditions apply to all supplied surgically prepared animals. Full copies are available on request Animals used for our surgical procedures, originate from Harlan Laboratories rodent barriers. Animals from these barriers meet the FELASA Recommendations 2002 (W.Nicklas et al). Recent Health Reports from the Harlan barriers located in Blackthorn and Hillcrest can be obtained from our website ( Surgery takes place under aseptic conditions minimizing the risk of microbiological contamination. After surgery the operated animals stay at our surgical unit for one more week in order to recover, making them fit to travel to the customer. Surgical Services Additional information In order to fully monitor the successful recovery of animals from surgery, we allow at least one week before shipping. An animal diary with the history of the perioperative care and instructions for care taking of the animals (e.g. flushing the cannula s, special water substitutions etc) after delivery is included. Procedures which are not listed above can be made available upon special request or can be especially developed. Surgical procedures do not include the price of the animal, shipping, or container charges. Although all precautions are taken and the risk is minimal, Harlan can not be held liable for the microbiological health status at time of shipment, after the surgery and recovery. Harlan Laboratories is using skilled technicians and aseptic conditions to perform the requested surgical services. In case of dissatisfaction with the services supplied for a valid reason, liability will be limited. Harlan makes no representation or warranty express or implied, concerning the performed surgery. Contact us at [email protected] for pricing and additional information For every surgical procedure, we require a justtification of home office authority and a Project License number. Although information provided in this document is limited to rodents, Harlan Laboratories is offering these services also in larger species, including dogs. Contact your local account manager for additional information. tel + (0) fax + (0) 1 2 [email protected]

44 Transgenic Services Transgenic Services Harlan provides the biomedical research community with a range of services combining rederivation and transgenic strain development with high throughput molecular genetic screening technology, as well as general genetic services. To initiate rederivation, we request a minimum of males and 10 females at breeding age. If animal availability is limited, colony expansion is available to meet this requirement. Standard rederivation service includes health monitoring (serology, bacteriology, parasitology, pathology and PCR (i.e. Helicobacter spp) of recipient females. Expansion rederivation includes mating of the rederived nucleus and additional health monitoring of two rederived offspring. Other Harlan Services Include: Genotyping Standard Polymerase Chain Reaction (PCR) Quantitative PCR (QPCR) Single Nucleotide Polymorphism (SNP) Detection Speed Congenic Services Purify your mouse genomes to avoid experimental variables Speed up your backcrossing procedure from 10 to generations Genotyping of each generation using microsatellites or SNPs analysis Clear genetic background characterization of the colony founders before their delivery to your facility Maintenance of your animals in microbiological controlled area in IVC racks or isolators Mouse Embryo Cryopreservation Eliminates maintenance of colonies to sustain available research models Reallocates production space and associated resources to other areas of research priority Preserves the genetic integrity of models for future development Insurance against physical, genetic and pathologic disasters Harvest of early stage embryos Standard number of 00 embryos; other numbers dependent upon client requirements Embryo storage in two geographically separate locations or returned to the client Rodent Rederivation Embryo or hysterectomy rederivation from breeders obtained from the donating institution Health status evaluation using clientapproved microbiologic monitoring profiles on foster or recipient females and/or offspring Eliminates pathogenic and opportunistic microorganisms Eliminates distribution restrictions to collaborating investigators Eliminates variables that affect research results Offspring delivered to the client or maintained by Harlan in flexiblefilm isolators for colony expansion Inbred Strain Verification Microsatellite Marker Testing SNP Profiling Creation of chimera s Colony development ES Cells Microinjection Generation of chimeras Colony development Visit our website or contact us at [email protected] for pricing and detailed information on all our transgenic services The Harlan Advantage Full import and export services State of the art technologies employed Global availability of services Quarantine facilities Dedicated project managers One price, even if a project must be repeated to obtain positive outcome

45 Colony Production And Maintenance Colony Production & Maintenance Maintenance in flexiblefilm isolators protects health and genetic integrity Custom breeding protocols Health status evaluation using clientapproved microbiologic monitoring profiles Genetic monitoring and tissue sampling services Reallocates client production space and associated resources to other areas of research priority Delivery to clients in companyowned, environmentally controlled vehicles Coordinates animal shipments to collaborating investigators Importation and Quarantine Import coordination of domestic and international shipments Maintenance in flexiblefilm isolators protects health and genetic integrity Protocols designed for both breeding and nonbreeding quarantine procedures Health testing evaluation of sentinel or imported colony cohorts using clientapproved microbiologic test profiles Genetic testing available Treatment of pathogens during quarantine Delivery to clients in companyowned, environmentally controlled vehicles Eliminates clients risk of receiving unknown pathogen positive animals Protects health integrity of requesting institution from incoming animals Reallocates space, labor and other institutional resources Predefined or extended quarantine periods Distribution or production as required by requesting institution Prices available on request Flexiblefilm isolators Harlan Isotec is an industry leader in the development of quality and diversified applications. Customized to meet our customers requirements, our complete line of isolators ranges from small labtop to very large units. Application of Isotec Systems Production of laboratory animals up to germfree (axenic) status in a stable environment for long periods of time Maintenance of animals involved in longterm studies where a consistent, uniform environment is desired Maintenance of pathogenpositive animals in a pathogenfree environment Features include: 2tier system offered for full economic utilization of available space HEPA filters Individual air supply Pressure differential gauge continuously monitors pressure Manoeuverable freestanding mobile racking with lockable wheels Isotec isolators offer: Quarantine of transgenic rodent models Protection of immunodeficient rodent models Small labtop isolators ( rat or 1 mouse cages) Large units (0 rat or 10 mouse cages) Banked units ( separate miniisolators combined) Hysterectomy suites, surgical units Easy to use and portable Accessories Assembly, customer training and consultations Spare parts and technical support Access to isolator design personnel Colony Production and Maintenance Contact us at [email protected] for pricing and detailed information on the full range of isolators and accessories The Harlan Advantage Safe maintenance of your transgenic lines Total flexibility in design Use your own cages Models ranging from 10 to 200 mouse cages Isolator training for technicians Free consultation with Harlan inhouse expert tel + (0) fax + (0) 1 2 [email protected]

46 Ordering Information Ordering Information How to Order Orders may be placed by mail, telephone, facsimile or . Mail: Harlan Laboratories, U.K. Ltd. Station Road Blackthorn, Bicester, Oxon OX2 1TP, England Tel: + (0) Fax: + (0) 1 2 Purchase order numbers must be supplied with each order, they must show the correct name, age, weight and sex of the animals desired. Standing orders are encouraged to ensure an adequate supply of the animals you require. Harlan Laboratories U.K. Ltd cannot accept responsibility for duplicate orders caused by confirmations which are not marked clearly. Harlan Laboratories U.K. Ltd cannot accept any liability for orders which have been received verbally and have not been confirmed in writing by mail, facsimile or . Additional Stocks and Strains, Special requests: Please call us for availability for pricing on strains not listed. We will work with you to develop colonies to meet your requirements. Shipping Harlan Laboratories U.K. Ltd operates it's own fleet of environmentally controlled trucks. Harlan Laboratories U.K. Ltd employ their own drivers who are specially trained in laboratory animal care to ensure your animals are delivered in the best possible condition. Cancellation Policy All Species This is an agreement between Harlan Laboratories U.K. Ltd and the customer with a confirmed P.O for animals to be delivered on a specific date. (Time mated orders will include specification on mating dates/gestation dates/delivery dates). If a confirmed order/standing order is cancelled less than weeks prior to the delivery date, Harlan Laboratories U.K. Ltd will apply a 100% cancellation charge (animal value only). Harlan Laboratories U.K. Ltd also reserves the right to cancel or vary any order for any cause beyond its control. Postponement Policy Dogs All orders which are postponed will incur a administrative charge as detailed: 1. First postponement to incur an admin charge of 0 per dog. 2. Second postponement to incur an admin charge of 100 per dog.. Third postponement would incur a full cancellation charge and the order cancelled automatically. Maximum duration a postponed order is allowed to move is weeks. Enquiry/Reservation This is an agreement between Harlan Laboratories U.K. Ltd and the customer and relates to an Enquiry/Reservation only. The offer given by the Customer Services Representative will only remain open for a period of working days from the time of the original offer. The customer will be advised that their reservation will end without any intervention after working days. It will not be the responsibility of Harlan Laboratories U.K. Ltd Customer Services Representative to contact the customer back prior to releasing the Enquiry/Reservation. Therefore if no further instruction is received from the customer their reservation will be released automatically. TimeMated Policy Rodents only Harlan Laboratories U.K. Ltd has established procedures in all production facilities to produce pregnant animals. (Certain strains of Rats and Mice) Timed pregnant Rats and Mice are determined by the observation of a vaginal plug. Harlan Laboratories U.K. Ltd use an Impedance Meter for determining the stage of oestrus in Rats only. Plug date is considered to be day zero (0) of gestation. Rats and Mice are palpated to ensure pregnancy prior to packing. Due to the natural variation in the length of gestation, the exact day of parturition cannot be guaranteed. Expected pregnancy rate schedule Time mated Time mated Untimed < 1 days 1 days gestation pregnant 1 gestation and over days gestation Stock or Strain (at shipping) (at shipping) (at shipping) All Outbred Rats/Mice * 0% 0% ** All Inbred Rats/Mice * 0% 0% ** * Plug guarantee only; no guaranteed pregnancy. Plug date = Day 0. ** Untimed pregnant rodents will be selected from our breeding colonies on the basis of palpation or visual confirmation. A variation of to days gestation can be expected. Therefore Harlan can not be held responsible for actual gestation and / or exact day of littering To avoid charges, cancellations for time mated animals must be received one week prior to mating date. Pregnant rats and mice cannot be delivered after day 1 of gestation to comply with UK Guidelines. What day does implantation occur? Implantation occurs about Day in the mouse and Day in the rat. We recommend that whenever possible, customers avoid orders which would ship animals during the time of implantation. Harlan Laboratories U.K. Ltd cannot guarantee the number of pups per litter. TimeMated Policy Rabbits only Timed pregnant Rabbits are determined by the observation of the mating. The mating date is considered to be day zero (0) of gestation. Due to the natural variation in the length of gestation, the exact day of parturition cannot be guaranteed. Pregnancy is not guaranteed even though the mating has been observed and recorded. Pregnant animals are transported in accordance with the (Animal (scientific procedures) Act 1) Code of practice for the housing and care of Animals in designated Breeding and supplying Establishment (Home office, 1). Harlan Laboratories U.K. Ltd cannot guarantee late term animals will not deliver in transit, and requests for credit or replacement of these animals may be declined. If problems regarding gestational age or pregnancy are encountered, customers should immediately contact Harlan Laboratories U.K. Ltd Customer Services Department and provide detailed information regarding the animals involved. Requests for a credit and/or replacement of these animals may be declined if appropriate documentation is not provided to us.

47 Growth Curves Growth curve data provided in this product guide should be used as a guideline only. Data can be subject to differences in environmental circumstances, such as housing conditions, type of diets, etc. Weight Specifications In the event that an order for animals includes a weight specification, Harlan will assume that such specification pertains to the packaging weight. The client must take this into account when placing an order. It is known that animals may experience weight changes during transport. Depending on the age, sex and developmental status of the animal and duration of the transport itself, animals might lose or gain weight during transport. In almost all cases, animals will return to their weight at shipping within 2 hrs after arrival. This statement has to be used as a guidance only, as the rate of weight recovery may be strainspecific and is also influenced by external factors, e.g. maintenance on arrival in a new facility, diet composition, position of individuals in a new animal hierachy. Contact our local office for animals required with a narrow defined weight range. Licences The customer shall be responsible for obtaining all necessary licences and approvals for use, or import, of any item purchased from Harlan Laboratories U.K. Ltd and for all necessary exchange control consents required in order to pay for goods. Reservation of Title All products remain the property of Harlan Laboratories U.K. Ltd until such time as full payment is received by Harlan Laboratories U.K. Ltd. Full copies of our general Harlan terms and conditions are available on request. Terms and Conditions Terms and Conditions Prices and Terms All prices quoted do not include VAT. VAT will be applied to invoices in accordance with the UK legislation at the tax point date. Prices are quoted in pounds sterling and are subject to change without notice. Terms are nett 0 days (0 days in the case of export orders). Unless otherwise requested, shipping charges will be added to your invoice. There is an additional charge for expedited services. Delivery At all times, Harlan Laboratories U.K. Ltd will try to honour delivery dates/times, but no guarantee is given or implied that specific delivery dates will be met. Export Orders Export orders currently are zero rated for VAT purposes. Conditions Because of the nature of our products, returns cannot be accepted. Harlan Laboratories U.K. Ltd will, at its election, replace or refund the purchase price of animals which do not conform to the customers written specifications. Harlan Laboratories U.K. Ltd must be notified of a complaint of any kind within two days of receipt of the order. Customers must provide the purchase order number, invoice number and any other relevant detail. Harlan Laboratories U.K. Ltd shall not in any case be liable for specific, incidental or consequential damages of any kind. No warranty or guarantee, other than that which is specifically given, can be assumed, or implied, since the ultimate conditions and variability of use are beyond Harlan Laboratories U.K. Ltd control. The Validity, performance and construction of these Conditions and of any transaction to which they relate shall be governed by English Law and both parties will accept the judgement of the English Courts. tel + (0) fax + (0) 1 2 [email protected]

48 Find out more We re Harlan Laboratories. And we re here to help you do research better. Contact your account manager or visit us on the Web at ww.harlan.com Corporate Headquarters Harlan Laboratories, Inc. 20 Allison Pointe Blvd., Suite 00 Indianapolis, IN Harlan Laboratories, Inc. Harlan, Harlan Laboratories, Helping you do research better, and the Harlan logo are trademarks of Harlan Laboratories, Inc.