Strain Name:

B6.129X1(FVB)-Nr1h4tm1Gonz/J

Stock Number:

007214

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Mice homozygous for this targeted mutant allele display a proatherogenic serum lipoprotein profile characterized by elevated levels of serum and hepatic cholesterol and triglycerides. This mutant mouse strain represents a model that may be useful in studies related to bile acid and lipid homeostasis.

Description

Strain Information

Former Names B6.129X(FVB)-Nr1h4tm1Gonz/J    (Changed: 16-MAY-08 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   14-MAY-08
Specieslaboratory mouse
GenerationN10F5 (11-APR-11)
Generation Definitions
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Mice that are homozygous for the targeted Nr1h4 allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Nr1h4 protein product is detected in liver tissue although an aberrant transcript appears to be generated. Homozygous mice display a proatherogenic serum lipoprotein profile characterized by elevated levels of serum and hepatic cholesterol and triglycerides. Serum bile acids are also elevated. When fed a diet supplemented with 1% cholic acid, severe wasting, hypothermia and increased mortality is observed. Wildtype mice fed a similar diet display no ill effects. Levels of fecal bile excretion are reduced in homozygotes. This mutant mouse strain represents a model that may be useful in studies related to bile acid and lipid homeostasis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the exon encoding the ligand-binding domain (nts 1238-1779). A loxP site was placed 5' of the targeted exon. The neomycin resistance and thymidine kinase genes were flanked by loxP sites and placed 3' of the targeted exon. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells from Genome Systems Inc. (St. Louis, MO). Correctly targeted ES cells were injected into C57BL/6N blastocysts. The resulting chimeric animals were crossed to female C57BL/6N mice. Progeny animals were mated with heterozygous transgenic mice expressing Cre recombinase (EIIA promoter) on a pure FVB background. Offspring bearing the recombined Nr1h4 allele, but not the Cre transgene were obtained. The mice were then backcrossed to C57BL/6J for 5 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Nr1h4tm1Gonz allele
004144   STOCK Nr1h4tm1Gonz/J
View Strains carrying   Nr1h4tm1Gonz     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Hepatocellular Carcinoma
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Nr1h4tm1Gonz/Nr1h4tm1Gonz

        involves: 129X1/SvJ * C57BL/6N
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • about 30% of mutants die by day 7 when placed on a 1% cholic acid diet   (MGI Ref ID J:64792)
  • growth/size/body phenotype
  • decreased body weight
    • body weight is about 20% less than in wild-type mice, regardless of age   (MGI Ref ID J:121075)
    • cachexia
      • mutants on a 1% cholic acid diet exhibit severe wasting   (MGI Ref ID J:64792)
  • decreased susceptibility to weight gain
    • mutants on a 1% cholic acid diet exhibit a progressive decrease in body weight that results in about 1/3 of the initial body weight by day 5 of the diet   (MGI Ref ID J:64792)
  • homeostasis/metabolism phenotype
  • abnormal bile salt homeostasis
    • mutants on a regular diet and 1% cholic acid diet have fecal bile acid excretion about 2-fold and 4-fold, respectively, lower than in wild-type   (MGI Ref ID J:64792)
    • mutants on a 1% cholic acid diet exhibit higher (7-fold) urinary bile acid excretion rates than wild-type on the same diet   (MGI Ref ID J:64792)
    • abnormal bile salt level
      • mutants on a regular diet exhibit an 8-fold increase in total serum bile acid concentration   (MGI Ref ID J:64792)
      • mutants on a 1% cholic acid diet exhibit an 23-fold increase in total serum bile acid concentration   (MGI Ref ID J:64792)
      • mutants on a regular or 1% cholic acid diet have lower bile acid pool (about by 2 fold) than wild-type   (MGI Ref ID J:64792)
      • increased bile salt level
        • 3-fold and 5.6-fold increase in serum bile acid levels in young and older mutants, respectively, compared to wild-type mice   (MGI Ref ID J:121075)
        • hepatic bile acid levels are 2x as high as in wild-type mice at 12 months of age   (MGI Ref ID J:121075)
  • decreased body temperature
    • mutants on a 1% cholic acid diet exhibit hypothermia   (MGI Ref ID J:64792)
  • increased circulating cholesterol level
    • mutants on a regular diet or on a 1% cholesterol diet exhibit increased serum total cholesterol levels   (MGI Ref ID J:64792)
  • increased circulating phospholipid level
    • mutants on a regular diet or on a 1% cholesterol diet exhibit increased phospholipid levels   (MGI Ref ID J:64792)
  • increased circulating triglyceride level
    • mutants on a regular or a 1% cholesterol diet exhibit increased triglyceride levels   (MGI Ref ID J:64792)
  • increased liver cholesterol level
    • mutants on a 1% cholesterol diet show 1.4-fold greater hepatic cholesterol levels   (MGI Ref ID J:64792)
  • increased liver triglyceride level
    • mutants on a regular diet show 2.2-fold greater hepatic triglyceride levels   (MGI Ref ID J:64792)
    • mutants on a 1% cholesterol diet show 2.4-fold greater hepatic triglyceride levels   (MGI Ref ID J:64792)
  • liver/biliary system phenotype
  • abnormal liver morphology
    • mutants on a 1% cholic acid diet exhibit liver lesions indicative of severe hepatotoxicity, with numerous vacuolated and necrotic cells   (MGI Ref ID J:64792)
    • enlarged liver
      • liver size, as a percentage of body weight, is higher than in wild-type mice at 12 months of age   (MGI Ref ID J:121075)
    • hepatic steatosis
      • mutants on a regular diet or a 1% cholesterol diet exhibit more lipid containing vacuoles in the liver than wild-type   (MGI Ref ID J:64792)
    • increased liver cholesterol level
      • mutants on a 1% cholesterol diet show 1.4-fold greater hepatic cholesterol levels   (MGI Ref ID J:64792)
    • increased liver triglyceride level
      • mutants on a regular diet show 2.2-fold greater hepatic triglyceride levels   (MGI Ref ID J:64792)
      • mutants on a 1% cholesterol diet show 2.4-fold greater hepatic triglyceride levels   (MGI Ref ID J:64792)
  • increased hepatocyte apoptosis
    • mutants exhibit an increase in hepatocyte apoptosis as indicated by an increase in TUNEL staining; 3 month old mutants show a higher level of apoptosis than 12 month old mutants   (MGI Ref ID J:121075)
  • increased hepatocyte proliferation
    • BrdU labeling indicates increased hepatocyte proliferation at 3 months of age compared to wild-type mice; at 12 months of age, proliferation has decreased but is still significantly higher than in controls   (MGI Ref ID J:121075)
  • cellular phenotype
  • increased hepatocyte apoptosis
    • mutants exhibit an increase in hepatocyte apoptosis as indicated by an increase in TUNEL staining; 3 month old mutants show a higher level of apoptosis than 12 month old mutants   (MGI Ref ID J:121075)
  • increased hepatocyte proliferation
    • BrdU labeling indicates increased hepatocyte proliferation at 3 months of age compared to wild-type mice; at 12 months of age, proliferation has decreased but is still significantly higher than in controls   (MGI Ref ID J:121075)
  • tumorigenesis
  • increased liver tumor incidence
    • 64% of mutants at 12 months of age display preneoplastic foci   (MGI Ref ID J:121075)
    • 38% total tumor incidence in 12 month old mutants; older mice were not analyzed for further tumor incidence   (MGI Ref ID J:121075)
    • both male and female mutants have liver lesions at 12 months of age; degenerative lesions consist of hypertrophic and eosinophilic hepatocytes accompanied by proliferating oval cells and lipid disposition   (MGI Ref ID J:121075)
    • 9% of mutants at 12 months of age develop mixed tumors consisting of hepatocellular carcinoma and hepatocholangiocellular carcinoma; mixed tumor involves a fibrous stroma and immune cell infiltrate, ductile formation and fibrosis   (MGI Ref ID J:121075)
    • increased hepatocellular carcinoma incidence
      • 6% of mutants at 12 months of age develop hepatocellular carcinoma   (MGI Ref ID J:121075)
    • increased liver adenoma incidence
      • 36% of mutants at 12 months of age develop hepatocellular adenomas   (MGI Ref ID J:121075)

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

Nr1h4tm1Gonz/Nr1h4tm1Gonz

        involves: 129/Sv
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • normal plasma levels of testosterone   (MGI Ref ID J:118368)

Nr1h4tm1Gonz/Nr1h4tm1Gonz

        involves: 129X1/SvJ
  • liver/biliary system phenotype
  • abnormal bile composition
    • the increase in the bile acid pool consists of increases in cholate and its derivates including taurocholic acid and taurodeoxycholic acid while other bile acids are found at normal levels   (MGI Ref ID J:129978)
  • homeostasis/metabolism phenotype
  • increased bile salt level
    • serum bile acids are greatly elevated in these mice   (MGI Ref ID J:129978)
    • total bile acid pool collected from liver, gallbladder and small intestine is almost 2.5-fold higher than in controls   (MGI Ref ID J:129978)
    • the increases in the bile acid pool consist of increases in cholate and its derivates including taurocholic acid and taurodeoxycholic acid   (MGI Ref ID J:129978)
  • increased circulating cholesterol level
    • total cholesterol levels in serum are about double that found in wild-type mice   (MGI Ref ID J:129978)
  • increased circulating triglyceride level
    • serum triglyceride levels are significantly higher than in control mice   (MGI Ref ID J:129978)

Nr1h4tm1Gonz/Nr1h4tm1Gonz

        STOCK Nr1h4tm1Gonz/J
  • homeostasis/metabolism phenotype
  • increased circulating alanine transaminase level   (MGI Ref ID J:149005)
  • increased circulating aspartate transaminase level   (MGI Ref ID J:149005)
  • increased circulating cholesterol level   (MGI Ref ID J:149005)
  • increased circulating triglyceride level   (MGI Ref ID J:149005)

Nr1h4tm1Gonz/Nr1h4tm1Gonz

        involves: 129X1/SvJ * C57BL/6
  • liver/biliary system phenotype
  • abnormal liver morphology
    • starting at 9 months of age, some mutants display preneoplasms in the liver, with small foci becoming obvious at 12 months of age   (MGI Ref ID J:118204)
    • liver damage includes many vaculoles due to lipid deposits, vaculation due to cell damage, inflammation, and focal necrosis   (MGI Ref ID J:118204)
    • significant amounts of BrdU+ cells are detected around the damaged regions of the liver suggesting initiation of a compensatory regenerative proliferation   (MGI Ref ID J:118204)
    • enlarged liver
      • enlarged liver is not completely due to tumor formation because hepatomegaly is seen before tumors are observed   (MGI Ref ID J:118204)
    • focal hepatic necrosis   (MGI Ref ID J:118204)
  • increased hepatocyte apoptosis
    • TUNEL staining indicates increased hepatocyte apoptosis as mutants age   (MGI Ref ID J:118204)
  • liver inflammation   (MGI Ref ID J:118204)
  • tumorigenesis
  • increased liver tumor incidence
    • both males and females develop liver tumors at 15 months of age of varying severity   (MGI Ref ID J:118204)
    • mutants fed a diet containing 2% cholestyramine, a bile acid-sequestering resin, for 3 months starting at 11 months of age when they do not have tumors, have a significantly reduced number and size of liver malignant lesions when they are older   (MGI Ref ID J:118204)
    • increased hepatocellular carcinoma incidence
      • tumors are typical hepatocellular adenoma and carcinoma   (MGI Ref ID J:118204)
    • increased liver adenoma incidence
      • tumors are typical hepatocellular adenoma and carcinoma   (MGI Ref ID J:118204)
  • cellular phenotype
  • increased hepatocyte apoptosis
    • TUNEL staining indicates increased hepatocyte apoptosis as mutants age   (MGI Ref ID J:118204)
  • homeostasis/metabolism phenotype
  • increased bile salt level
    • serum and liver bile acid levels are higher in aging mutants than in wild-type controls   (MGI Ref ID J:118204)
  • increased circulating aspartate transaminase level
    • levels of alanine aminotransferase (ALT) are much higher in aging mutants than in controls, indicating increased liver damage   (MGI Ref ID J:118204)
  • immune system phenotype
  • liver inflammation   (MGI Ref ID J:118204)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Internal/Organ Research
Liver Defects

Metabolism Research
Lipid Metabolism

Nr1h4tm1Gonz related

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nr1h4tm1Gonz
Allele Name targeted mutation 1, Frank Gonzalez
Allele Type Targeted (knock-out)
Common Name(s) FXR/BAR -; FXR-; FXRalpha-; Fxrtm1Gonz;
Mutation Made ByDr. Frank Gonzalez,   National Institutes of Health
Strain of Origin129X1/SvJ
Gene Symbol and Name Nr1h4, nuclear receptor subfamily 1, group H, member 4
Chromosome 10
Gene Common Name(s) AI957360; BAR; FXR; Fxr; HRR-1; HRR1; RIP14; Rxrip14; expressed sequence AI957360; farnesoid X receptor; retinoid X receptor interacting protein 14;
General Note The ES cell line was not specified, but was purchased from Genome Systems (St. Louis, MO). (Note added 7/26/01: Genome Systems was bought by Incyte.)
Molecular Note Mice with a targeted deletion of the last exon encoding the ligand binding domain and all of the 3' untranslated region were produced as follows: A loxP site was inserted in the intron 5' to the last exon and a loxP-flanked neomycin cassette was inserted 3' to the last exon. After production of chimeric founder mice, F1 mice were mated to Tg(EIIa-Cre)1Lmgd mice to produce offspring that carried a recombined deletion of the last exon and neomycin cassette. No Nr1h4 protein product is detected in liver tissue from these null mice although an aberrant transcript appears to be generated. [MGI Ref ID J:64792]

Genotyping

Genotyping Information

Genotyping Protocols

Nr1h4tm1Gonz, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sinal CJ; Tohkin M; Miyata M; Ward JM; Lambert G; Gonzalez FJ. 2000. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis Cell 102(6):731-44. [PubMed: 11030617]  [MGI Ref ID J:64792]

Additional References

Nr1h4tm1Gonz related

Abdelkarim M; Caron S; Duhem C; Prawitt J; Dumont J; Lucas A; Bouchaert E; Briand O; Brozek J; Kuipers F; Fievet C; Cariou B; Staels B. 2010. The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferator-activated receptor-gamma and interfering with the Wnt/beta-catenin pathways. J Biol Chem 285(47):36759-67. [PubMed: 20851881]  [MGI Ref ID J:167021]

Allen K; Jaeschke H; Copple BL. 2011. Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol 178(1):175-86. [PubMed: 21224055]  [MGI Ref ID J:168234]

Anakk S; Bhosale M; Schmidt VA; Johnson RL; Finegold MJ; Moore DD. 2013. Bile acids activate YAP to promote liver carcinogenesis. Cell Rep 5(4):1060-9. [PubMed: 24268772]  [MGI Ref ID J:205595]

Anakk S; Watanabe M; Ochsner SA; McKenna NJ; Finegold MJ; Moore DD. 2011. Combined deletion of Fxr and Shp in mice induces Cyp17a1 and results in juvenile onset cholestasis. J Clin Invest 121(1):86-95. [PubMed: 21123943]  [MGI Ref ID J:171856]

Boyer JL; Trauner M; Mennone A; Soroka CJ; Cai SY; Moustafa T; Zollner G; Lee JY; Ballatori N. 2006. Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol 290(6):G1124-30. [PubMed: 16423920]  [MGI Ref ID J:111085]

Cariou B; Bouchaert E; Abdelkarim M; Dumont J; Caron S; Fruchart JC; Burcelin R; Kuipers F; Staels B. 2007. FXR-deficiency confers increased susceptibility to torpor. FEBS Lett 581(27):5191-8. [PubMed: 17950284]  [MGI Ref ID J:127752]

Cariou B; van Harmelen K; Duran-Sandoval D; van Dijk T; Grefhorst A; Bouchaert E; Fruchart JC; Gonzalez FJ; Kuipers F; Staels B. 2005. Transient impairment of the adaptive response to fasting in FXR-deficient mice. FEBS Lett 579(19):4076-80. [PubMed: 16023103]  [MGI Ref ID J:100327]

Cariou B; van Harmelen K; Duran-Sandoval D; van Dijk TH; Grefhorst A; Abdelkarim M; Caron S; Torpier G; Fruchart JC; Gonzalez FJ; Kuipers F; Staels B. 2006. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 281(16):11039-49. [PubMed: 16446356]  [MGI Ref ID J:110560]

Cheng X; Klaassen CD. 2008. Critical role of PPAR-alpha in perfluorooctanoic acid- and perfluorodecanoic acid-induced downregulation of Oatp uptake transporters in mouse livers. Toxicol Sci 106(1):37-45. [PubMed: 18703564]  [MGI Ref ID J:142114]

Cheng X; Klaassen CD. 2008. Perfluorocarboxylic acids induce cytochrome P450 enzymes in mouse liver through activation of PPAR-alpha and CAR transcription factors. Toxicol Sci 106(1):29-36. [PubMed: 18648086]  [MGI Ref ID J:141993]

Chennamsetty I; Claudel T; Kostner KM; Baghdasaryan A; Kratky D; Levak-Frank S; Frank S; Gonzalez FJ; Trauner M; Kostner GM. 2011. Farnesoid X receptor represses hepatic human APOA gene expression. J Clin Invest 121(9):3724-34. [PubMed: 21804189]  [MGI Ref ID J:178263]

Cui YJ; Aleksunes LM; Tanaka Y; Goedken MJ; Klaassen CD. 2009. Compensatory induction of liver efflux transporters in response to ANIT-induced liver injury is impaired in FXR-null mice. Toxicol Sci 110(1):47-60. [PubMed: 19407337]  [MGI Ref ID J:149881]

Cyphert HA; Ge X; Kohan AB; Salati LM; Zhang Y; Hillgartner FB. 2012. Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21. J Biol Chem 287(30):25123-38. [PubMed: 22661717]  [MGI Ref ID J:188851]

Deng Y; Wang H; Lu Y; Liu S; Zhang Q; Huang J; Zhu R; Yang J; Zhang R; Zhang D; Shen W; Ning G; Yang Y. 2013. Identification of chemerin as a novel FXR target gene down-regulated in the progression of nonalcoholic steatohepatitis. Endocrinology 154(5):1794-801. [PubMed: 23507574]  [MGI Ref ID J:197926]

Dufer M; Horth K; Wagner R; Schittenhelm B; Prowald S; Wagner TF; Oberwinkler J; Lukowski R; Gonzalez FJ; Krippeit-Drews P; Drews G. 2012. Bile acids acutely stimulate insulin secretion of mouse beta-cells via farnesoid X receptor activation and K(ATP) channel inhibition. Diabetes 61(6):1479-89. [PubMed: 22492528]  [MGI Ref ID J:196833]

Duran-Sandoval D; Cariou B; Percevault F; Hennuyer N; Grefhorst A; van Dijk TH; Gonzalez FJ; Fruchart JC; Kuipers F; Staels B. 2005. The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition. J Biol Chem 280(33):29971-9. [PubMed: 15899888]  [MGI Ref ID J:101042]

Fickert P; Fuchsbichler A; Moustafa T; Wagner M; Zollner G; Halilbasic E; Stoger U; Arrese M; Pizarro M; Solis N; Carrasco G; Caligiuri A; Sombetzki M; Reisinger E; Tsybrovskyy O; Zatloukal K; Denk H; Jaeschke H; Pinzani M; Trauner M. 2009. Farnesoid X receptor critically determines the fibrotic response in mice but is expressed to a low extent in human hepatic stellate cells and periductal myofibroblasts. Am J Pathol 175(6):2392-405. [PubMed: 19910507]  [MGI Ref ID J:155300]

Guo GL; Lambert G; Negishi M; Ward JM; Brewer HB Jr; Kliewer SA; Gonzalez FJ; Sinal CJ. 2003. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem 278(46):45062-71. [PubMed: 12923173]  [MGI Ref ID J:129256]

Guo GL; Santamarina-Fojo S; Akiyama TE; Amar MJ; Paigen BJ; Brewer B Jr; Gonzalez FJ. 2006. Effects of FXR in foam-cell formation and atherosclerosis development. Biochim Biophys Acta 1761(12):1401-9. [PubMed: 17110163]  [MGI Ref ID J:118172]

Gutierrez A; Ratliff EP; Andres AM; Huang X; McKeehan WL; Davis RA. 2006. Bile acids decrease hepatic paraoxonase 1 expression and plasma high-density lipoprotein levels via FXR-mediated signaling of FGFR4. Arterioscler Thromb Vasc Biol 26(2):301-6. [PubMed: 16284190]  [MGI Ref ID J:118817]

Hanniman EA; Lambert G; McCarthy TC; Sinal CJ. 2005. Loss of functional farnesoid X receptor increases atherosclerotic lesions in apolipoprotein E-deficient mice. J Lipid Res 46(12):2595-604. [PubMed: 16186601]  [MGI Ref ID J:106149]

Hartman HB; Lai K; Evans MJ. 2009. Loss of small heterodimer partner expression in the liver protects against dyslipidemia. J Lipid Res 50(2):193-203. [PubMed: 18820241]  [MGI Ref ID J:149005]

Houten SM; Volle DH; Cummins CL; Mangelsdorf DJ; Auwerx J. 2007. In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue. Mol Endocrinol 21(6):1312-23. [PubMed: 17426284]  [MGI Ref ID J:121836]

Huang W; Ma K; Zhang J; Qatanani M; Cuvillier J; Liu J; Dong B; Huang X; Moore DD. 2006. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 312(5771):233-6. [PubMed: 16614213]  [MGI Ref ID J:108344]

Hubbert ML; Zhang Y; Lee FY; Edwards PA. 2007. Regulation of hepatic Insig-2 by the farnesoid X receptor. Mol Endocrinol 21(6):1359-69. [PubMed: 17440045]  [MGI Ref ID J:121842]

Iakova P; Timchenko L; Timchenko NA. 2011. Intracellular signaling and hepatocellular carcinoma. Semin Cancer Biol 21(1):28-34. [PubMed: 20850540]  [MGI Ref ID J:170790]

Inagaki T; Moschetta A; Lee YK; Peng L; Zhao G; Downes M; Yu RT; Shelton JM; Richardson JA; Repa JJ; Mangelsdorf DJ; Kliewer SA. 2006. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci U S A 103(10):3920-5. [PubMed: 16473946]  [MGI Ref ID J:107133]

Inoue J; Satoh S; Kita M; Nakahara M; Hachimura S; Miyata M; Nishimaki-Mogami T; Sato R. 2008. PPARalpha gene expression is up-regulated by LXR and PXR activators in the small intestine. Biochem Biophys Res Commun 371(4):675-8. [PubMed: 18448072]  [MGI Ref ID J:136213]

Jansen PL. 2007. Endogenous bile acids as carcinogens. J Hepatol 47(3):434-5. [PubMed: 17624466]  [MGI Ref ID J:126534]

Jung D; Mangelsdorf DJ; Meyer UA. 2006. Pregnane X receptor is a target of farnesoid X receptor. J Biol Chem 281(28):19081-91. [PubMed: 16682417]  [MGI Ref ID J:114858]

Kim I; Ahn SH; Inagaki T; Choi M; Ito S; Guo GL; Kliewer SA; Gonzalez FJ. 2007. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J Lipid Res 48(12):2664-72. [PubMed: 17720959]  [MGI Ref ID J:129978]

Kim I; Morimura K; Shah Y; Yang Q; Ward JM; Gonzalez FJ. 2007. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 28(5):940-6. [PubMed: 17183066]  [MGI Ref ID J:121075]

Lambert G; Amar MJ; Guo G; Brewer HB Jr; Gonzalez FJ; Sinal CJ. 2003. The Farnesoid X-receptor Is an Essential Regulator of Cholesterol Homeostasis. J Biol Chem 278(4):2563-70. [PubMed: 12421815]  [MGI Ref ID J:81724]

Langhi C; Pedraz-Cuesta E; Donate Y; Marrero PF; Haro D; Rodriguez JC. 2013. Regulation of N-Myc downstream regulated gene 2 by bile acids. Biochem Biophys Res Commun 434(1):102-9. [PubMed: 23541942]  [MGI Ref ID J:201212]

Lee FY; de Aguiar Vallim TQ; Chong HK; Zhang Y; Liu Y; Jones SA; Osborne TF; Edwards PA. 2010. Activation of the farnesoid X receptor provides protection against acetaminophen-induced hepatic toxicity. Mol Endocrinol 24(8):1626-36. [PubMed: 20573685]  [MGI Ref ID J:182859]

Lee H; Hubbert ML; Osborne TF; Woodford K; Zerangue N; Edwards PA. 2007. Regulation of the sodium/sulfate co-transporter by farnesoid X receptor alpha. J Biol Chem 282(30):21653-61. [PubMed: 17545158]  [MGI Ref ID J:124601]

Lee H; Zhang Y; Lee FY; Nelson SF; Gonzalez FJ; Edwards PA. 2006. FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine. J Lipid Res 47(1):201-14. [PubMed: 16251721]  [MGI Ref ID J:106031]

Li G; Thomas AM; Williams JA; Kong B; Liu J; Inaba Y; Xie W; Guo GL. 2012. Farnesoid X receptor induces murine scavenger receptor Class B type I via intron binding. PLoS One 7(4):e35895. [PubMed: 22540009]  [MGI Ref ID J:187197]

Li J; Pircher PC; Schulman IG; Westin SK. 2005. Regulation of complement C3 expression by the bile acid receptor FXR. J Biol Chem 280(9):7427-34. [PubMed: 15590640]  [MGI Ref ID J:105051]

Li T; Francl JM; Boehme S; Ochoa A; Zhang Y; Klaassen CD; Erickson SK; Chiang JY. 2012. Glucose and insulin induction of bile acid synthesis: mechanisms and implication in diabetes and obesity. J Biol Chem 287(3):1861-73. [PubMed: 22144677]  [MGI Ref ID J:180806]

Lian F; Xing X; Yuan G; Schafer C; Rauser S; Walch A; Rocken C; Ebeling M; Wright MB; Schmid RM; Ebert MP; Burgermeister E. 2011. Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage. Biochem J 438(2):315-23. [PubMed: 21619550]  [MGI Ref ID J:177893]

Liu B; Ramirez CM; Miller AM; Repa JJ; Turley SD; Dietschy JM. 2010. Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid. J Lipid Res 51(5):933-44. [PubMed: 19965601]  [MGI Ref ID J:160197]

Ma K; Saha PK; Chan L; Moore DD. 2006. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest 116(4):1102-9. [PubMed: 16557297]  [MGI Ref ID J:107809]

Ma K; Xiao R; Tseng HT; Shan L; Fu L; Moore DD. 2009. Circadian dysregulation disrupts bile Acid homeostasis. PLoS One 4(8):e6843. [PubMed: 19718444]  [MGI Ref ID J:152389]

Marschall HU; Wagner M; Bodin K; Zollner G; Fickert P; Gumhold J; Silbert D; Fuchsbichler A; Sjovall J; Trauner M. 2006. Fxr(-/-) mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids. J Lipid Res 47(3):582-92. [PubMed: 16327028]  [MGI Ref ID J:107554]

Martin LJ; Tremblay JJ. 2010. Nuclear receptors in leydig cell gene expression and function. Biol Reprod 83(1):3-14. [PubMed: 20375256]  [MGI Ref ID J:161974]

Mencarelli A; Renga B; Distrutti E; Fiorucci S. 2009. Antiatherosclerotic effect of farnesoid X receptor. Am J Physiol Heart Circ Physiol 296(2):H272-81. [PubMed: 19028791]  [MGI Ref ID J:146332]

Mencarelli A; Renga B; Migliorati M; Cipriani S; Distrutti E; Santucci L; Fiorucci S. 2009. The bile acid sensor farnesoid X receptor is a modulator of liver immunity in a rodent model of acute hepatitis. J Immunol 183(10):6657-66. [PubMed: 19880446]  [MGI Ref ID J:157169]

Miyata M; Matsuda Y; Nomoto M; Takamatsu Y; Sato N; Hamatsu M; Dawson PA; Gonzalez FJ; Yamazoe Y. 2009. Cholesterol feeding prevents hepatic accumulation of bile acids in cholic acid-fed farnesoid X receptor (FXR)-null mice: FXR-independent suppression of intestinal bile acid absorption. Drug Metab Dispos 37(2):338-44. [PubMed: 18988759]  [MGI Ref ID J:163803]

Modica S; Murzilli S; Salvatore L; Schmidt DR; Moschetta A. 2008. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res 68(23):9589-94. [PubMed: 19047134]  [MGI Ref ID J:142094]

Moschetta A; Bookout AL; Mangelsdorf DJ. 2004. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med 10(12):1352-8. [PubMed: 15558057]  [MGI Ref ID J:94664]

Nomoto M; Miyata M; Yin S; Kurata Y; Shimada M; Yoshinari K; Gonzalez FJ; Suzuki K; Shibasaki S; Kurosawa T; Yamazoe Y. 2009. Bile acid-induced elevated oxidative stress in the absence of farnesoid X receptor. Biol Pharm Bull 32(2):172-8. [PubMed: 19182371]  [MGI Ref ID J:151031]

Popescu IR; Helleboid-Chapman A; Lucas A; Vandewalle B; Dumont J; Bouchaert E; Derudas B; Kerr-Conte J; Caron S; Pattou F; Staels B. 2010. The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity. FEBS Lett 584(13):2845-51. [PubMed: 20447400]  [MGI Ref ID J:161322]

Prawitt J; Abdelkarim M; Stroeve JH; Popescu I; Duez H; Velagapudi VR; Dumont J; Bouchaert E; van Dijk TH; Lucas A; Dorchies E; Daoudi M; Lestavel S; Gonzalez FJ; Oresic M; Cariou B; Kuipers F; Caron S; Staels B. 2011. Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes 60(7):1861-71. [PubMed: 21593203]  [MGI Ref ID J:186756]

Ratliff EP; Gutierrez A; Davis RA. 2006. Transgenic expression of CYP7A1 in LDL receptor-deficient mice blocks diet-induced hypercholesterolemia. J Lipid Res 47(7):1513-20. [PubMed: 16609145]  [MGI Ref ID J:112052]

Renga B; Mencarelli A; Cipriani S; D'Amore C; Carino A; Bruno A; Francisci D; Zampella A; Distrutti E; Fiorucci S. 2013. The bile acid sensor FXR is required for immune-regulatory activities of TLR-9 in intestinal inflammation. PLoS One 8(1):e54472. [PubMed: 23372731]  [MGI Ref ID J:195920]

Renga B; Mencarelli A; Cipriani S; D'Amore C; Zampella A; Monti MC; Distrutti E; Fiorucci S. 2011. The nuclear receptor FXR regulates hepatic transport and metabolism of glutamine and glutamate. Biochim Biophys Acta 1812(11):1522-31. [PubMed: 21757002]  [MGI Ref ID J:180347]

Renga B; Mencarelli A; D'Amore C; Cipriani S; Baldelli F; Zampella A; Distrutti E; Fiorucci S. 2012. Glucocorticoid receptor mediates the gluconeogenic activity of the farnesoid X receptor in the fasting condition. FASEB J 26(7):3021-31. [PubMed: 22447981]  [MGI Ref ID J:187477]

Renga B; Migliorati M; Mencarelli A; Cipriani S; D'Amore C; Distrutti E; Fiorucci S. 2011. Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4 promoter. Biochim Biophys Acta 1809(3):157-65. [PubMed: 21296199]  [MGI Ref ID J:182376]

Rizzo G; Disante M; Mencarelli A; Renga B; Gioiello A; Pellicciari R; Fiorucci S. 2006. The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo. Mol Pharmacol 70(4):1164-73. [PubMed: 16778009]  [MGI Ref ID J:135714]

Sayin SI; Wahlstrom A; Felin J; Jantti S; Marschall HU; Bamberg K; Angelin B; Hyotylainen T; Oresic M; Backhed F. 2013. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 17(2):225-35. [PubMed: 23395169]  [MGI Ref ID J:196606]

Schmidt DR; Holmstrom SR; Fon Tacer K; Bookout AL; Kliewer SA; Mangelsdorf DJ. 2010. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J Biol Chem 285(19):14486-94. [PubMed: 20233723]  [MGI Ref ID J:164561]

Sekiya S; Suzuki A. 2011. Glycogen synthase kinase 3{beta}-dependent Snail degradation directs hepatocyte proliferation in normal liver regeneration. Proc Natl Acad Sci U S A 108(27):11175-80. [PubMed: 21690373]  [MGI Ref ID J:174303]

Seyer P; Vallois D; Poitry-Yamate C; Schutz F; Metref S; Tarussio D; Maechler P; Staels B; Lanz B; Grueter R; Decaris J; Turner S; da Costa A; Preitner F; Minehira K; Foretz M; Thorens B. 2013. Hepatic glucose sensing is required to preserve beta cell glucose competence. J Clin Invest 123(4):1662-76. [PubMed: 23549084]  [MGI Ref ID J:197607]

Shih DM; Kast-Woelbern HR; Wong J; Xia YR; Edwards PA; Lusis AJ. 2006. A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids. J Lipid Res 47(2):384-92. [PubMed: 16269825]  [MGI Ref ID J:107566]

Shimizu M; Li J; Maruyama R; Inoue J; Sato R. 2013. FGF19 (fibroblast growth factor 19) as a novel target gene for activating transcription factor 4 in response to endoplasmic reticulum stress. Biochem J 450(1):221-9. [PubMed: 23205607]  [MGI Ref ID J:194178]

Stedman C; Liddle C; Coulter S; Sonoda J; Alvarez JG; Evans RM; Downes M. 2006. Benefit of farnesoid X receptor inhibition in obstructive cholestasis. Proc Natl Acad Sci U S A 103(30):11323-8. [PubMed: 16844773]  [MGI Ref ID J:111798]

Vavassori P; Mencarelli A; Renga B; Distrutti E; Fiorucci S. 2009. The bile acid receptor FXR is a modulator of intestinal innate immunity. J Immunol 183(10):6251-61. [PubMed: 19864602]  [MGI Ref ID J:157174]

Volle DH; Duggavathi R; Magnier BC; Houten SM; Cummins CL; Lobaccaro JM; Verhoeven G; Schoonjans K; Auwerx J. 2007. The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice. Genes Dev 21(3):303-15. [PubMed: 17289919]  [MGI Ref ID J:118368]

Wang C; Zhang F; Wang L; Zhang Y; Li X; Huang K; Du M; Liu F; Huang S; Guan Y; Huang D; Huang K. 2013. Poly(ADP-ribose) polymerase 1 promotes oxidative-stress-induced liver cell death via suppressing farnesoid X receptor alpha. Mol Cell Biol 33(22):4492-503. [PubMed: 24043304]  [MGI Ref ID J:206095]

Wang XX; Jiang T; Shen Y; Caldas Y; Miyazaki-Anzai S; Santamaria H; Urbanek C; Solis N; Scherzer P; Lewis L; Gonzalez FJ; Adorini L; Pruzanski M; Kopp JB; Verlander JW; Levi M. 2010. Diabetic nephropathy is accelerated by farnesoid X receptor deficiency and inhibited by farnesoid X receptor activation in a type 1 diabetes model. Diabetes 59(11):2916-27. [PubMed: 20699418]  [MGI Ref ID J:169616]

Wang YD; Yang F; Chen WD; Huang X; Lai L; Forman BM; Huang W. 2008. Farnesoid x receptor protects liver cells from apoptosis induced by serum deprivation in vitro and fasting in vivo. Mol Endocrinol 22(7):1622-32. [PubMed: 18436567]  [MGI Ref ID J:136910]

Williams JA; Thomas AM; Li G; Kong B; Zhan L; Inaba Y; Xie W; Ding WX; Guo GL. 2012. Tissue specific induction of p62/Sqstm1 by farnesoid X receptor. PLoS One 7(8):e43961. [PubMed: 22952826]  [MGI Ref ID J:191657]

Yamamoto Y; Moore R; Hess HA; Guo GL; Gonzalez FJ; Korach KS; Maronpot RR; Negishi M. 2006. Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. J Biol Chem 281(24):16625-31. [PubMed: 16606610]  [MGI Ref ID J:113721]

Yang F; Huang X; Yi T; Yen Y; Moore DD; Huang W. 2007. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res 67(3):863-7. [PubMed: 17283114]  [MGI Ref ID J:118204]

Yu L; Gupta S; Xu F; Liverman AD; Moschetta A; Mangelsdorf DJ; Repa JJ; Hobbs HH; Cohen JC. 2005. Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J Biol Chem 280(10):8742-7. [PubMed: 15611112]  [MGI Ref ID J:128570]

Zhang L; Huang X; Meng Z; Dong B; Shiah S; Moore DD; Huang W. 2009. Significance and Mechanism of CYP7a1 Gene Regulation during the Acute Phase of Liver Regeneration. Mol Endocrinol 23(2):137-45. [PubMed: 19056864]  [MGI Ref ID J:144235]

Zhang X; Huang S; Gao M; Liu J; Jia X; Han Q; Zheng S; Miao Y; Li S; Weng H; Xia X; Du S; Wu W; Gustafsson JA; Guan Y. 2014. Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice. Proc Natl Acad Sci U S A 111(6):2277-82. [PubMed: 24464484]  [MGI Ref ID J:206661]

Zhang Y; Castellani LW; Sinal CJ; Gonzalez FJ; Edwards PA. 2004. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev 18(2):157-69. [PubMed: 14729567]  [MGI Ref ID J:87780]

Zhang Y; Lee FY; Barrera G; Lee H; Vales C; Gonzalez FJ; Willson TM; Edwards PA. 2006. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A 103(4):1006-11. [PubMed: 16410358]  [MGI Ref ID J:105654]

Zhang Y; Wang X; Vales C; Lee FY; Lee H; Lusis AJ; Edwards PA. 2006. FXR deficiency causes reduced atherosclerosis in Ldlr-/- mice. Arterioscler Thromb Vasc Biol 26(10):2316-21. [PubMed: 16825595]  [MGI Ref ID J:128055]

Zhang Y; Yin L; Anderson J; Ma H; Gonzalez FJ; Willson TM; Edwards PA. 2010. Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia. J Biol Chem 285(5):3035-43. [PubMed: 19996107]  [MGI Ref ID J:159763]

Zollner G; Wagner M; Fickert P; Geier A; Fuchsbichler A; Silbert D; Gumhold J; Zatloukal K; Kaser A; Tilg H; Denk H; Trauner M. 2005. Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver. Am J Physiol Gastrointest Liver Physiol 289(5):G798-805. [PubMed: 16002565]  [MGI Ref ID J:104772]

Zollner G; Wagner M; Moustafa T; Fickert P; Silbert D; Gumhold J; Fuchsbichler A; Halilbasic E; Denk H; Marschall HU; Trauner M. 2006. Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids. Am J Physiol Gastrointest Liver Physiol 290(5):G923-32. [PubMed: 16357057]  [MGI Ref ID J:111080]

van Erpecum KJ; Wang DQ; Moschetta A; Ferri D; Svelto M; Portincasa P; Hendrickx JJ; Schipper M; Calamita G. 2006. Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function. J Lipid Res 47(1):32-41. [PubMed: 16224116]  [MGI Ref ID J:106039]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as homozygotes.
Mating SystemHomozygote x Homozygote         (Female x Male)   14-MAY-08
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $195.00Female or MaleHomozygous for Nr1h4tm1Gonz  
Price per Pair (US dollars $)Pair Genotype
$390.00Homozygous for Nr1h4tm1Gonz x Homozygous for Nr1h4tm1Gonz  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $253.50Female or MaleHomozygous for Nr1h4tm1Gonz  
Price per Pair (US dollars $)Pair Genotype
$507.00Homozygous for Nr1h4tm1Gonz x Homozygous for Nr1h4tm1Gonz  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

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

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See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

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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JAX® Mice
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Terms of Use


General Terms and Conditions


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phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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