Strain Name:

B6.CBA-Tg(CETP)5203Tall/J

Stock Number:

003904

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Xian-cheng Jiang,   Columbia University

Description
Mice carrying the human CETP minigene under the control of its own promoter show a marked increase in CETP mRNA in liver when mice are fed a high fat, high cholesterol diet. Less dramatic increases are observed in spleen, small intestine and adipose tissues. Elevated plasma CETP protein levels are also observed. Mice carrying human CETP show reduced levels of plasma high density lipoprotein. This strain has been a useful model in studies related to cholesterol metabolism.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of CETP
001929   C57BL/6-Tg(CETP)UCTP20Pnu/J
View Strains carrying other alleles of CETP     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Hyperalphalipoproteinemia 1; HALP1   (CETP)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Tg(CETP)5203Tall/0

        involves: C57BL/6 * CBA/J
  • homeostasis/metabolism phenotype
  • abnormal lipid level
    • hepatic cholesteryl ester level is lower than in Apoc1-defcient mice   (MGI Ref ID J:117482)
    • abnormal phospholipid level
      • biliary level is decreased compared to Apoc1-deficient mice   (MGI Ref ID J:117482)
    • decreased cholesterol level
      • biliary level is decreased compared to Apoc1-deficient mice   (MGI Ref ID J:117482)
    • decreased liver triglyceride level
      • hepatic levels are significantly lower than in Apoc1-deficient mice   (MGI Ref ID J:117482)
  • liver/biliary system phenotype
  • decreased liver triglyceride level
    • hepatic levels are significantly lower than in Apoc1-deficient mice   (MGI Ref ID J:117482)

Tg(CETP)5203Tall/0

        involves: C57BL/6J * CBA/J
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • despite being fed an atherogenic diet, mice exhibit no change in total cholesterol, triglyceride and HDL-cholesterol levels compared to similarly treated wild-type mice   (MGI Ref ID J:128254)
    • decreased circulating HDL cholesterol level
      • compared to in Apobec1tm1Chan homozygotes and wild-type mice   (MGI Ref ID J:48202)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(CETP)5203Tall
Allele Name transgene insertion 5203, Alan Tall
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) CETP; NFR-CETP;
Mutation Made By Xian-cheng Jiang,   Columbia University
Strain of Origin(C57BL/6J x CBA/J)F1
Expressed Gene CETP, cholesteryl ester transfer protein, plasma, human
Promoter CETP, cholesteryl ester transfer protein, plasma, human
General Note Transgenic mice on a genetic background that involves C57BL/6J and CBA/J show a marked increase in CETP mRNA in liver when mice are fed a high fat, high cholesterol diet. Less dramatic increases are observed in spleen, small intestine and adipose tissues. Elevated plasma CETP protein levels are also observed.
Molecular Note The transgene contains the human CETP mini gene under the control of its own promoter. The mini gene consists of 3.2 Kb of 5' flanking sequence, exons 1-2 and 13-16, and 2.0 Kb of 3' flanking sequence. [MGI Ref ID J:69181]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(CETP)5203Tall-Alternate 1,

MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Jiang XC; Agellon LB; Walsh A; Breslow JL; Tall A. 1992. Dietary cholesterol increases transcription of the human cholesteryl ester transfer protein gene in transgenic mice. Dependence on natural flanking sequences. J Clin Invest 90(4):1290-5. [PubMed: 1401066]  [MGI Ref ID J:69181]

Additional References

Masucci-Magoulas L; Moulin P; Jiang XC; Richardson H; Walsh A; Breslow JL; Tall A. 1995. Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice. J Clin Invest 95(4):1587-94. [PubMed: 7706465]  [MGI Ref ID J:93801]

Tg(CETP)5203Tall related

Auvinen HE; Wang Y; Princen H; Romijn JA; Havekes LM; Smit JW; Meijer OC; Biermasz NR; Rensen PC; Pereira AM. 2013. Both transient and continuous corticosterone excess inhibit atherosclerotic plaque formation in APOE*3-leiden.CETP mice. PLoS One 8(5):e63882. [PubMed: 23717502]  [MGI Ref ID J:200720]

Berti JA; Amaral ME; Boschero AC; Nunes VS; Harada LM; Castilho LN; Oliveira HC. 2001. Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice. Metabolism 50(5):530-6. [PubMed: 11319713]  [MGI Ref ID J:69090]

Berti JA; de Faria EC; Oliveira HC. 2005. Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes. Braz J Med Biol Res 38(3):391-8. [PubMed: 15761619]  [MGI Ref ID J:128254]

Casquero AC; Berti JA; Salerno AG; Bighetti EJ; Cazita PM; Ketelhuth DF; Gidlund M; Oliveira HC. 2006. Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP expression in transgenic mice. J Lipid Res 47(7):1526-34. [PubMed: 16603720]  [MGI Ref ID J:112057]

Cazita PM; Berti JA; Aoki C; Gidlund M; Harada LM; Nunes VS; Quintao EC; Oliveira HC. 2003. Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice. J Lipid Res 44(1):33-40. [PubMed: 12518020]  [MGI Ref ID J:120685]

Cheema SK; Agarwal-Mawal A; Murray CM; Tucker S. 2005. Lack of stimulation of cholesteryl ester transfer protein by cholesterol in the presence of a high-fat diet. J Lipid Res 46(11):2356-66. [PubMed: 16106052]  [MGI Ref ID J:104777]

Cheema SK; Rashid-Kolvear F. 2003. Streptozotocin-induced increase in cholesterol ester transfer protein (CETP) and its reversal by insulin in transgenic mice expressing human CETP. Can J Physiol Pharmacol 81(10):997-1004. [PubMed: 14608418]  [MGI Ref ID J:136412]

El Bouhassani M; Gilibert S; Moreau M; Saint-Charles F; Treguier M; Poti F; Chapman MJ; Le Goff W; Lesnik P; Huby T. 2011. Cholesteryl Ester Transfer Protein Expression Partially Attenuates the Adverse Effects of SR-BI Receptor Deficiency on Cholesterol Metabolism and Atherosclerosis. J Biol Chem 286(19):17227-38. [PubMed: 21454568]  [MGI Ref ID J:172678]

Fontana K; Campos GE; Staron RS; da Cruz-Hofling MA. 2013. Effects of anabolic steroids and high-intensity aerobic exercise on skeletal muscle of transgenic mice. PLoS One 8(11):e80909. [PubMed: 24260508]  [MGI Ref ID J:209673]

Gautier T; Masson D; Jong MC; Pais de Barros JP; Duverneuil L; Le Guern N; Deckert V; Dumont L; Bataille A; Zak Z; Jiang XC; Havekes LM; Lagrost L. 2005. Apolipoprotein CI overexpression is not a relevant strategy to block cholesteryl ester transfer protein (CETP) activity in CETP transgenic mice. Biochem J 385(Pt 1):189-95. [PubMed: 15339254]  [MGI Ref ID J:117536]

Gautier T; Tietge UJ; Boverhof R; Perton FG; Le Guern N; Masson D; Rensen PC; Havekes LM; Lagrost L; Kuipers F. 2007. Hepatic lipid accumulation in apolipoprotein C-I-deficient mice is potentiated by cholesteryl ester transfer protein. J Lipid Res 48(1):30-40. [PubMed: 17053273]  [MGI Ref ID J:117482]

Geerling JJ; Boon MR; van der Zon GC; van den Berg SA; van den Hoek AM; Lombes M; Princen HM; Havekes LM; Rensen PC; Guigas B. 2014. Metformin lowers plasma triglycerides by promoting VLDL-triglyceride clearance by brown adipose tissue in mice. Diabetes 63(3):880-91. [PubMed: 24270984]  [MGI Ref ID J:209084]

Hildebrand RB; Lammers B; Meurs I; Korporaal SJ; De Haan W; Zhao Y; Kruijt JK; Pratico D; Schimmel AW; Holleboom AG; Hoekstra M; Kuivenhoven JA; Van Berkel TJ; Rensen PC; Van Eck M. 2010. Restoration of high-density lipoprotein levels by cholesteryl ester transfer protein expression in scavenger receptor class B type I (SR-BI) knockout mice does not normalize pathologies associated with SR-BI deficiency. Arterioscler Thromb Vasc Biol 30(7):1439-45. [PubMed: 20431066]  [MGI Ref ID J:180862]

Hime NJ; Black AS; Bulgrien JJ; Curtiss LK. 2008. Leukocyte-derived hepatic lipase increases HDL and decreases en face aortic atherosclerosis in LDLr-/- mice expressing CETP. J Lipid Res 49(10):2113-23. [PubMed: 18599739]  [MGI Ref ID J:140426]

Hirata H; Yimin; Segawa S; Ozaki M; Kobayashi N; Shigyo T; Chiba H. 2012. Xanthohumol prevents atherosclerosis by reducing arterial cholesterol content via CETP and apolipoprotein E in CETP-transgenic mice. PLoS One 7(11):e49415. [PubMed: 23166663]  [MGI Ref ID J:195463]

Hoekstra M; Ye D; Hildebrand RB; Zhao Y; Lammers B; Stitzinger M; Kuiper J; Van Berkel TJ; Van Eck M. 2009. Scavenger receptor class B type I-mediated uptake of serum cholesterol is essential for optimal adrenal glucocorticoid production. J Lipid Res 50(6):1039-46. [PubMed: 19179307]  [MGI Ref ID J:149859]

Jiang XC; Tall AR; Qin S; Lin M; Schneider M; Lalanne F; Deckert V; Desrumaux C; Athias A; Witztum JL; Lagrost L. 2002. Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E. J Biol Chem 277(35):31850-6. [PubMed: 12105225]  [MGI Ref ID J:120468]

Kawano K; Qin SC; Lin M; Tall AR; Jiang Xc. 2000. Cholesteryl ester transfer protein and phospholipid transfer protein have nonoverlapping functions in vivo J Biol Chem 275(38):29477-81. [PubMed: 10893412]  [MGI Ref ID J:64848]

Li Z; Wang Y; van der Sluis RJ; van der Hoorn JW; Princen HM; Van Eck M; Van Berkel TJ; Rensen PC; Hoekstra M. 2012. Niacin reduces plasma CETP levels by diminishing liver macrophage content in CETP transgenic mice. Biochem Pharmacol 84(6):821-9. [PubMed: 22750059]  [MGI Ref ID J:192404]

Lie J; Moerland M; van Gent T; van Haperen R; Scheek L; Sadeghi-Niaraki F; de Crom R; van Tol A. 2006. Sex differences in atherosclerosis in mice with elevated phospholipid transfer protein activity are related to decreased plasma high density lipoproteins and not to increased production of triglycerides. Biochim Biophys Acta 1761(9):1070-7. [PubMed: 16935026]  [MGI Ref ID J:116584]

MacLean PS; Bower JF; Vadlamudi S; Osborne JN; Bradfield JF; Burden HW; Bensch WH; Kauffman RF; Barakat HA. 2003. Cholesteryl ester transfer protein expression prevents diet-induced atherosclerotic lesions in male db/db mice. Arterioscler Thromb Vasc Biol 23(8):1412-5. [PubMed: 12791674]  [MGI Ref ID J:109846]

Masucci-Magoulas L; Moulin P; Jiang XC; Richardson H; Walsh A; Breslow JL; Tall A. 1995. Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice. J Clin Invest 95(4):1587-94. [PubMed: 7706465]  [MGI Ref ID J:93801]

Masucci-Magoulas L; Plump A; Jiang XC; Walsh A; Breslow JL; Tall AR. 1996. Profound induction of hepatic cholesteryl ester transfer protein transgene expression in apolipoprotein E and low density lipoprotein receptor gene knockout mice. A novel mechanism signals changes in plasma cholesterol levels. J Clin Invest 97(1):154-61. [PubMed: 8550828]  [MGI Ref ID J:111394]

McLaren DG; Wang SP; Stout SJ; Xie D; Miller PL; Mendoza V; Rosa R; Castro-Perez J; Previs SF; Johns DG; Roddy TP. 2013. Tracking fatty acid kinetics in distinct lipoprotein fractions in vivo: a novel high-throughput approach for studying dyslipidemia in rodent models. J Lipid Res 54(1):276-81. [PubMed: 23042787]  [MGI Ref ID J:190918]

Nakamuta M; Taniguchi S; Ishida BY; Kobayashi K; Chan L. 1998. Phenotype interaction of apobec-1 and CETP, LDLR, and apoE gene expression in mice: role of apoB mRNA editing in lipoprotein phenotype expression. Arterioscler Thromb Vasc Biol 18(5):747-55. [PubMed: 9598833]  [MGI Ref ID J:48202]

Plump AS; Masucci-Magoulas L; Bruce C; Bisgaier CL; Breslow JL; Tall AR. 1999. Increased atherosclerosis in ApoE and LDL receptor gene knock-out mice as a result of human cholesteryl ester transfer protein transgene expression. Arterioscler Thromb Vasc Biol 19(4):1105-10. [PubMed: 10195942]  [MGI Ref ID J:55980]

Salerno AG; Patricio PR; Berti JA; Oliveira HC. 2009. Cholesteryl ester transfer protein (CETP) increases postprandial triglyceridaemia and delays triacylglycerol plasma clearance in transgenic mice. Biochem J 419(3):629-34. [PubMed: 19191759]  [MGI Ref ID J:149787]

Salerno AG; Silva TR; Amaral ME; Alberici LC; Bonfleur ML; Patricio PR; Francesconi EP; Grassi-Kassisse DM; Vercesi AE; Boschero AC; Oliveira HC. 2007. Overexpression of apolipoprotein CIII increases and CETP reverses diet-induced obesity in transgenic mice. Int J Obes (Lond) 31(10):1586-95. [PubMed: 17471296]  [MGI Ref ID J:151293]

Van Eck M; Ye D; Hildebrand RB; Kar Kruijt J; de Haan W; Hoekstra M; Rensen PC; Ehnholm C; Jauhiainen M; Van Berkel TJ. 2007. Important role for bone marrow-derived cholesteryl ester transfer protein in lipoprotein cholesterol redistribution and atherosclerotic lesion development in LDL receptor knockout mice. Circ Res 100(5):678-85. [PubMed: 17293475]  [MGI Ref ID J:133704]

Westerterp M; van der Hoogt CC; de Haan W; Offerman EH; Dallinga-Thie GM; Jukema JW; Havekes LM; Rensen PC. 2006. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice. Arterioscler Thromb Vasc Biol 26(11):2552-9. [PubMed: 16946130]  [MGI Ref ID J:128047]

Zhou H; Li Z; Silver DL; Jiang XC. 2006. Cholesteryl ester transfer protein (CETP) expression enhances HDL cholesteryl ester liver delivery, which is independent of scavenger receptor BI, LDL receptor related protein and possibly LDL receptor. Biochim Biophys Acta 1761(12):1482-8. [PubMed: 17055779]  [MGI Ref ID J:118151]

de Haan W; de Vries-van der Weij J; Mol IM; Hoekstra M; Romijn JA; Jukema JW; Havekes LM; Princen HM; Rensen PC. 2009. PXR agonism decreases plasma HDL levels in ApoE3-Leiden.CETP mice. Biochim Biophys Acta 1791(3):191-7. [PubMed: 19150509]  [MGI Ref ID J:148609]

van der Hoogt CC; de Haan W; Westerterp M; Hoekstra M; Dallinga-Thie GM; Romijn JA; Princen HM; Jukema JW; Havekes LM; Rensen PC. 2007. Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer protein expression. J Lipid Res 48(8):1763-71. [PubMed: 17525476]  [MGI Ref ID J:123774]

van der Hoorn JW; de Haan W; Berbee JF; Havekes LM; Jukema JW; Rensen PC; Princen HM. 2008. Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice. Arterioscler Thromb Vasc Biol 28(11):2016-22. [PubMed: 18669886]  [MGI Ref ID J:159800]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryThis strain arose on a (C57BL/6J x CBA/J)F1 background and has been backcrossed to C57BL/6 for at least ten generations (1/01)Coat color expected from breeding:Black

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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