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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator David Mangelsdorf,   UT Southwestern Medical Center

Description
Homozygous Nr1h3 (nuclear receptor subfamily 1, group H, member 3) targeted mutation mice lose their ability to respond normally to dietary cholesterol. Mice maintained on cholesterol diets fail to induce transcription of the Cyp7a1 (cytochrome P450, family 7, subfamily a, polypeptide 1) gene, a rate-limiting enzyme in bile acid synthesis, and fail to induce expression of ABCG5 (ATP-binding cassette, sub-family G (WHITE), member 5) and ABCG8 (ATP-binding cassette, sub-family G (WHITE), member 8), ATP-binding cassette transporters that are required for cholesterol secretion into bile. Large amounts of cholesterol rapidly accumulate in the liver leading to impaired hepatic function. Impaired reverse cholesterol transport from peripheral tissues is also observed. The ability to regulate lipids and carbohydrates is also lost. Defects in innate immune responses by activated macrophages have also been described. Males are not infertile, but show a significantly higher number of testicular apoptotic cells than wildtype mice. Testosterone production is significantly lower. It is not known whether genetic background affects the phenotype associated with this mutation.

Development
Exons 3-6, containing the complete DNA-binding domain and majority of the ligand-binding domain, were replaced with a neomycin resistance cassette. The mutation was created in SM1 embryonic stem (ES) cells derived from 129S6/SvEvTac mice. This strain was maintained on a mixed C57BL/6 and 129 genetic background by the donating laboratory.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying   Nr1h3^tm1Djm allele

013762	129-Nr1h3tm1Djm/J
013761	B6.129S6-Nr1h3tm1Djm/J

View Strains carrying   Nr1h3^tm1Djm     (2 strains)

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).

Ovarian Hyperstimulation Syndrome

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Nr1h3^tm1Djm/Nr1h3^tm1Djm

        involves: 129S6/SvEvTac * C57BL/6

• mortality/aging
• increased sensitivity to induced morbidity/mortality
  • mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls   (MGI Ref ID J:81696)
• reproductive system phenotype
• abnormal corpus luteum morphology
  • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• abnormal male germ cell apoptosis
  • apoptosis of germ cells within seminiferous tubules is more than double that of controls   (MGI Ref ID J:120913)
• abnormal ovary physiology
  • following follicle retrieval, a greater number of follicles are expulsed with 45% dead oocytes or empty zonae pellucidae unlike in similarly treated wild-type mice   (MGI Ref ID J:158168)
• • ovary hemorrhage
    • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• abnormal superovulation
  • superovulated-mice exhibit increased follicle expulsion, increased number of dead oocytes or empty zona pellucida, enlarged ovaries, ovarian cysts, rare ovarian hemorrhage, increased ovarian vascular permeability, circulating estradiol, and inflammation compared with similarly treated wild-type mice   (MGI Ref ID J:158168)
• enlarged ovary
  • following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice   (MGI Ref ID J:158168)
  • however, estradiol-treated mice have normal sized ovaries   (MGI Ref ID J:158168)
• ovary cysts
  • superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• homeostasis/metabolism phenotype
• abnormal bile salt homeostasis
  • mice fail to increase their pool of bile acid in response to a high cholesterol diet as wild-type mice do   (MGI Ref ID J:47971)
  • less fecal excretion of bile acid occurs in mice fed the high cholesterol diet compared to control mice   (MGI Ref ID J:47971)
  • the ratio of cholic acid to muricholic acid within the bile acid pool is significantly higher than controls on a chow-fed diet, and does not decrease when fed a high cholesterol diet   (MGI Ref ID J:47971)
• decreased circulating luteinizing hormone level
  • plasma LH levels are almost half that of controls   (MGI Ref ID J:120913)
• decreased circulating testosterone level
  • testosterone production in the testes is significantly reduced compared to controls   (MGI Ref ID J:120913)
• increased circulating alanine transaminase level
  • serum alanine transaminase levels are increased in mice that are fed a high cholesterol diet   (MGI Ref ID J:47971)
• increased circulating aspartate transaminase level
  • serum aspartate transaminase levels are increased in mice that are fed a high cholesterol diet   (MGI Ref ID J:47971)
• increased circulating cholesterol level
  • there is a 15- to 20- fold increase in liver cholesterol levels 7 days after being switched to a high (2%) cholesterol diet while only a modest increase is observed in control mice   (MGI Ref ID J:47971)
  • when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet   (MGI Ref ID J:47971)
• • increased circulating LDL cholesterol level
    • serum LDL levels are increased 5-fold in mice that are fed a high cholesterol diet   (MGI Ref ID J:47971)
• increased circulating estradiol level
  • superovulated-mice compared to in similarly treated wild-type   (MGI Ref ID J:158168)
• increased liver cholesterol level
  • there is a 15- to 20- fold increase in liver cholesterol levels 7 days after being switched to a high (2%) cholesterol diet while only a modest increase is observed in control mice   (MGI Ref ID J:47971)
  • when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet   (MGI Ref ID J:47971)
• liver/biliary system phenotype
• hepatic steatosis
  • on high (2%) cholesterol diets, livers develop fatty deposits that increase in number and size with time while control mice exhibit no abnormalities   (MGI Ref ID J:47971)
  • the liver appears pale and is double in size, inflammatory foci are developing, and signs of liver degeneration are evident after 3 months on the diet   (MGI Ref ID J:47971)
• increased liver cholesterol level
  • there is a 15- to 20- fold increase in liver cholesterol levels 7 days after being switched to a high (2%) cholesterol diet while only a modest increase is observed in control mice   (MGI Ref ID J:47971)
  • when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet   (MGI Ref ID J:47971)
• increased liver weight
  • 3 months on a high cholesterol diet leads to a doubling in liver mass without increasing body weight   (MGI Ref ID J:47971)
• liver degeneration
  • signs of liver degeneration are evident after 3 months on a high cholesterol diet   (MGI Ref ID J:47971)
  • increased serum levels of alanine and aspartate amino transferases are also indicitave of liver injury   (MGI Ref ID J:47971)
  • hepatocytes have lost most of their normal cell structure after 90 days on a high cholesterol diet   (MGI Ref ID J:47971)
• pale liver
  • liver appears white after 3 months on a high cholesterol diet due to presence of cholesterol filled droplets   (MGI Ref ID J:47971)
• cardiovascular system phenotype
• increased vascular permeability
  • in the ovaries of superovulated-mice compared to in similarly treated wild-type   (MGI Ref ID J:158168)
• ovary hemorrhage
  • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• immune system phenotype
• increased inflammatory response
  • following superovulation protocols, mice exhibit an increase in blood sediment rate compared with wild-type mice indicating inflammation   (MGI Ref ID J:158168)
• increased susceptibility to bacterial infection
  • mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls   (MGI Ref ID J:81696)
  • bacterial burden in the liver of day 2 of infection is 2 logs higher than controls   (MGI Ref ID J:81696)
• endocrine/exocrine gland phenotype
• abnormal corpus luteum morphology
  • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• abnormal ovary physiology
  • following follicle retrieval, a greater number of follicles are expulsed with 45% dead oocytes or empty zonae pellucidae unlike in similarly treated wild-type mice   (MGI Ref ID J:158168)
• • ovary hemorrhage
    • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• enlarged ovary
  • following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice   (MGI Ref ID J:158168)
  • however, estradiol-treated mice have normal sized ovaries   (MGI Ref ID J:158168)
• ovary cysts
  • superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice   (MGI Ref ID J:158168)
• cellular phenotype
• abnormal male germ cell apoptosis
  • apoptosis of germ cells within seminiferous tubules is more than double that of controls   (MGI Ref ID J:120913)

View Research Applications

Research Applications

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

Cardiovascular Research
Hypercholesterolemia

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Macrophage defects

Internal/Organ Research
Liver Defects

Metabolism Research
Lipid Metabolism

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Nr1h3tm1Djm
Allele Name		targeted mutation 1, David J Mangelsdorf
Allele Type		Targeted (knock-out)
Common Name(s)		LXRalpha (-); Nr1h3-;
Mutation Made By		David Mangelsdorf,   UT Southwestern Medical Center
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Nr1h3, nuclear receptor subfamily 1, group H, member 3
Chromosome		2
Gene Common Name(s)		AU018371; LXR alpha; LXR-a; LXRA; LXRalpha; RLD-1; Unr1; expressed sequence AU018371; ubiquitously-expressed nuclear receptor 1;
Molecular Note		Exons 3-6 encoding the DNA-binding and ligand-binding domains (amino acids 87-327) were replaced with a neomycin resistance gene via homologous recombination. Northern blot and Western blot analysis of liver from homozygous mutant animals verified the absence of mRNA and protein expression. [MGI Ref ID J:47971]

Genotyping

Genotyping Information

Genotyping Protocols

Nr1h3^tm1Djm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Peet DJ; Turley SD; Ma W; Janowski BA; Lobaccaro JM; Hammer RE; Mangelsdorf DJ. 1998. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93(5):693-704. [PubMed: 9630215]  [MGI Ref ID J:47971]

Additional References

Nr1h3^tm1Djm related

A-Gonzalez N; Bensinger SJ; Hong C; Beceiro S; Bradley MN; Zelcer N; Deniz J; Ramirez C; Diaz M; Gallardo G; de Galarreta CR; Salazar J; Lopez F; Edwards P; Parks J; Andujar M; Tontonoz P; Castrillo A. 2009. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 31(2):245-58. [PubMed: 19646905]  [MGI Ref ID J:151872]

Bensinger SJ; Bradley MN; Joseph SB; Zelcer N; Janssen EM; Hausner MA; Shih R; Parks JS; Edwards PA; Jamieson BD; Tontonoz P. 2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134(1):97-111. [PubMed: 18614014]  [MGI Ref ID J:145492]

Bradley MN; Hong C; Chen M; Joseph SB; Wilpitz DC; Wang X; Lusis AJ; Collins A; Hseuh WA; Collins JL; Tangirala RK; Tontonoz P. 2007. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J Clin Invest 117(8):2337-46. [PubMed: 17657314]  [MGI Ref ID J:123957]

Cha JY; Repa JJ. 2007. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem 282(1):743-51. [PubMed: 17107947]  [MGI Ref ID J:154828]

Cui G; Qin X; Wu L; Zhang Y; Sheng X; Yu Q; Sheng H; Xi B; Zhang JZ; Zang YQ. 2011. Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J Clin Invest 121(2):658-70. [PubMed: 21266776]  [MGI Ref ID J:171827]

Cummins CL; Volle DH; Zhang Y; McDonald JG; Sion B; Lefrancois-Martinez AM; Caira F; Veyssiere G; Mangelsdorf DJ; Lobaccaro JM. 2006. Liver X receptors regulate adrenal cholesterol balance. J Clin Invest 116(7):1902-12. [PubMed: 16823488]  [MGI Ref ID J:111742]

Denechaud PD; Bossard P; Lobaccaro JM; Millatt L; Staels B; Girard J; Postic C. 2008. ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in mouse liver. J Clin Invest 118(3):956-64. [PubMed: 18292813]  [MGI Ref ID J:135655]

Erbay E; Babaev VR; Mayers JR; Makowski L; Charles KN; Snitow ME; Fazio S; Wiest MM; Watkins SM; Linton MF; Hotamisligil GS. 2009. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat Med 15(12):1383-91. [PubMed: 19966778]  [MGI Ref ID J:155873]

Henry-Berger J; Mouzat K; Baron S; Bernabeu C; Marceau G; Saru JP; Sapin V; Lobaccaro JM; Caira F. 2008. Endoglin (CD105) expression is regulated by the liver X receptor alpha (NR1H3) in human trophoblast cell line JAR. Biol Reprod 78(6):968-75. [PubMed: 18276933]  [MGI Ref ID J:140815]

Hernandez Vallejo SJ; Alqub M; Luquet S; Cruciani-Guglielmacci C; Delerive P; Lobaccaro JM; Kalopissis AD; Chambaz J; Rousset M; Lacorte JM. 2009. Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet. Am J Physiol Gastrointest Liver Physiol 296(4):G782-92. [PubMed: 19196952]  [MGI Ref ID J:149786]

Hong C; Bradley MN; Rong X; Wang X; Wagner A; Grijalva V; Castellani LW; Salazar J; Realegeno S; Boyadjian R; Fogelman AM; Van Lenten BJ; Reddy ST; Lusis AJ; Tangirala RK; Tontonoz P. 2012. LXRalpha is uniquely required for maximal reverse cholesterol transport and atheroprotection in ApoE-deficient mice. J Lipid Res 53(6):1126-33. [PubMed: 22454476]  [MGI Ref ID J:184910]

Hong C; Walczak R; Dhamko H; Bradley MN; Marathe C; Boyadjian R; Salazar JV; Tontonoz P. 2011. Constitutive activation of LXR in macrophages regulates metabolic and inflammatory gene expression: identification of ARL7 as a direct target. J Lipid Res 52(3):531-9. [PubMed: 21187453]  [MGI Ref ID J:173138]

Joseph SB; Bradley MN; Castrillo A; Bruhn KW; Mak PA; Pei L; Hogenesch J; O'connell RM; Cheng G; Saez E; Miller JF; Tontonoz P. 2004. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119(2):299-309. [PubMed: 15479645]  [MGI Ref ID J:93893]

Joseph SB; Castrillo A; Laffitte BA; Mangelsdorf DJ; Tontonoz P. 2003. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 9(2):213-9. [PubMed: 12524534]  [MGI Ref ID J:81696]

Kalaany NY; Gauthier KC; Zavacki AM; Mammen PP; Kitazume T; Peterson JA; Horton JD; Garry DJ; Bianco AC; Mangelsdorf DJ. 2005. LXRs regulate the balance between fat storage and oxidation. Cell Metab 1(4):231-44. [PubMed: 16054068]  [MGI Ref ID J:129844]

Komuves LG; Schmuth M; Fowler AJ; Elias PM; Hanley K; Man MQ; Moser AH; Lobaccaro JM; Williams ML; Mangelsdorf DJ; Feingold KR. 2002. Oxysterol stimulation of epidermal differentiation is mediated by liver X receptor-beta in murine epidermis. J Invest Dermatol 118(1):25-34. [PubMed: 11851872]  [MGI Ref ID J:89874]

Koroskenyi K; Duro E; Pallai A; Sarang Z; Kloor D; Ucker DS; Beceiro S; Castrillo A; Chawla A; Ledent CA; Fesus L; Szondy Z. 2011. Involvement of adenosine A2A receptors in engulfment-dependent apoptotic cell suppression of inflammation. J Immunol 186(12):7144-55. [PubMed: 21593381]  [MGI Ref ID J:175472]

Kotti TJ; Ramirez DM; Pfeiffer BE; Huber KM; Russell DW. 2006. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci U S A 103(10):3869-74. [PubMed: 16505352]  [MGI Ref ID J:107142]

Kumar N; Wang H; Liu D; Collins S. 2009. Liver X receptor is a regulator of orphan nuclear receptor NOR-1 gene transcription in adipocytes. Int J Obes (Lond) 33(5):519-24. [PubMed: 19238156]  [MGI Ref ID J:151278]

Laffitte BA; Repa JJ; Joseph SB; Wilpitz DC; Kast HR; Mangelsdorf DJ; Tontonoz P. 2001. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci U S A 98(2):507-12. [PubMed: 11149950]  [MGI Ref ID J:67239]

Le Martelot G; Claudel T; Gatfield D; Schaad O; Kornmann B; Sasso GL; Moschetta A; Schibler U. 2009. REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis. PLoS Biol 7(9):e1000181. [PubMed: 19721697]  [MGI Ref ID J:153064]

Lu W; Hisatsune A; Koga T; Kato K; Kuwahara I; Lillehoj EP; Chen W; Cross AS; Gendler SJ; Gewirtz AT; Kim KC. 2006. Cutting edge: enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice. J Immunol 176(7):3890-4. [PubMed: 16547220]  [MGI Ref ID J:129884]

Lund EG; Peterson LB; Adams AD; Lam MH; Burton CA; Chin J; Guo Q; Huang S; Latham M; Lopez JC; Menke JG; Milot DP; Mitnaul LJ; Rex-Rabe SE; Rosa RL; Tian JY; Wright SD; Sparrow CP. 2006. Different roles of liver X receptor alpha and beta in lipid metabolism: effects of an alpha-selective and a dual agonist in mice deficient in each subtype. Biochem Pharmacol 71(4):453-63. [PubMed: 16325781]  [MGI Ref ID J:105722]

Makoukji J; Shackleford G; Meffre D; Grenier J; Liere P; Lobaccaro JM; Schumacher M; Massaad C. 2011. Interplay between LXR and Wnt/{beta}-Catenin Signaling in the Negative Regulation of Peripheral Myelin Genes by Oxysterols. J Neurosci 31(26):9620-9. [PubMed: 21715627]  [MGI Ref ID J:174058]

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]

Mouzat K; Prod'homme M; Volle DH; Sion B; Dechelotte P; Gauthier K; Vanacker JM; Lobaccaro JM. 2007. Oxysterol nuclear receptor LXRbeta regulates cholesterol homeostasis and contractile function in mouse uterus. J Biol Chem 282(7):4693-701. [PubMed: 17166844]  [MGI Ref ID J:120923]

Mouzat K; Volat F; Baron S; Alves G; Pommier AJ; Volle DH; Marceau G; DeHaze A; Dechelotte P; Duggavathi R; Caira F; Lobaccaro JM. 2009. Absence of nuclear receptors for oxysterols liver X receptor induces ovarian hyperstimulation syndrome in mice. Endocrinology 150(7):3369-75. [PubMed: 19325005]  [MGI Ref ID J:158168]

Ouvrier A; Alves G; Damon-Soubeyrand C; Marceau G; Cadet R; Janny L; Brugnon F; Kocer A; Pommier A; Lobaccaro JM; Drevet JR; Saez F. 2011. Dietary cholesterol-induced post-testicular infertility. PLoS One 6(11):e26966. [PubMed: 22073227]  [MGI Ref ID J:180996]

Ouvrier A; Cadet R; Vernet P; Lallier B; Chardigny JM; Lobaccaro JM; Drevet JR; Saez F. 2009. LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell specific manner. J Lipid Res 50:1766-1775. [PubMed: 19395734]  [MGI Ref ID J:153781]

Pascual-Garcia M; Carbo JM; Leon T; Matalonga J; Out R; Van Berkel T; Sarrias MR; Lozano F; Celada A; Valledor AF. 2011. Liver X receptors inhibit macrophage proliferation through downregulation of cyclins D1 and B1 and cyclin-dependent kinases 2 and 4. J Immunol 186(8):4656-67. [PubMed: 21398609]  [MGI Ref ID J:172455]

Patel R; Patel M; Tsai R; Lin V; Bookout AL; Zhang Y; Magomedova L; Li T; Chan JF; Budd C; Mangelsdorf DJ; Cummins CL. 2011. LXRbeta is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice. J Clin Invest 121(1):431-41. [PubMed: 21123945]  [MGI Ref ID J:171854]

Repa JJ; Berge KE; Pomajzl C; Richardson JA; Hobbs H; Mangelsdorf DJ. 2002. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 277(21):18793-800. [PubMed: 11901146]  [MGI Ref ID J:76837]

Repa JJ; Liang G; Ou J; Bashmakov Y; Lobaccaro JM; Shimomura I; Shan B; Brown MS; Goldstein JL; Mangelsdorf DJ. 2000. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta Genes Dev 14(22):2819-30. [PubMed: 11090130]  [MGI Ref ID J:65994]

Repa JJ; Turley SD; Lobaccaro JA; Medina J; Li L; Lustig K; Shan B; Heyman RA; Dietschy JM; Mangelsdorf DJ. 2000. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers [see comments] Science 289(5484):1524-9. [PubMed: 10968783]  [MGI Ref ID J:64343]

Spann NJ; Garmire LX; McDonald JG; Myers DS; Milne SB; Shibata N; Reichart D; Fox JN; Shaked I; Heudobler D; Raetz CR; Wang EW; Kelly SL; Sullards MC; Murphy RC; Merrill AH Jr; Brown HA; Dennis EA; Li AC; Ley K; Tsimikas S; Fahy E; Subramaniam S; Quehenberger O; Russell DW; Glass CK. 2012. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151(1):138-52. [PubMed: 23021221]  [MGI Ref ID J:188262]

Tangirala RK; Bischoff ED; Joseph SB; Wagner BL; Walczak R; Laffitte BA; Daige CL; Thomas D; Heyman RA; Mangelsdorf DJ; Wang X; Lusis AJ; Tontonoz P; Schulman IG. 2002. Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc Natl Acad Sci U S A 99(18):11896-901. [PubMed: 12193651]  [MGI Ref ID J:125452]

Uemura A; Kusuhara S; Wiegand SJ; Yu RT; Nishikawa S. 2006. Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes. J Clin Invest 116(2):369-77. [PubMed: 16424942]  [MGI Ref ID J:105463]

Umetani M; Domoto H; Gormley AK; Yuhanna IS; Cummins CL; Javitt NB; Korach KS; Shaul PW; Mangelsdorf DJ. 2007. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13(10):1185-92. [PubMed: 17873880]  [MGI Ref ID J:129931]

Uppal H; Saini SP; Moschetta A; Mu Y; Zhou J; Gong H; Zhai Y; Ren S; Michalopoulos GK; Mangelsdorf DJ; Xie W. 2007. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. Hepatology 45(2):422-32. [PubMed: 17256725]  [MGI Ref ID J:136468]

Valasek MA; Clarke SL; Repa JJ. 2007. Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPC1L1 expression in mouse. J Lipid Res 48(12):2725-35. [PubMed: 17726195]  [MGI Ref ID J:129975]

Viennois E; Esposito T; Dufour J; Pommier A; Fabre S; Kemeny JL; Guy L; Morel L; Lobaccaro JM; Baron S. 2012. Lxralpha regulates the androgen response in prostate epithelium. Endocrinology 153(7):3211-23. [PubMed: 22547570]  [MGI Ref ID J:188637]

Volle DH; Mouzat K; Duggavathi R; Siddeek B; Dechelotte P; Sion B; Veyssiere G; Benahmed M; Lobaccaro JM. 2007. Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. Mol Endocrinol 21(5):1014-27. [PubMed: 17341595]  [MGI Ref ID J:120913]

Volle DH; Repa JJ; Mazur A; Cummins CL; Val P; Henry-Berger J; Caira F; Veyssiere G; Mangelsdorf DJ; Lobaccaro JM. 2004. Regulation of the aldo-keto reductase gene akr1b7 by the nuclear oxysterol receptor LXRalpha (liver X receptor-alpha) in the mouse intestine: putative role of LXRs in lipid detoxification processes. Mol Endocrinol 18(4):888-98. [PubMed: 14739254]  [MGI Ref ID J:89079]

Wang H; Zhang Y; Yehuda-Shnaidman E; Medvedev AV; Kumar N; Daniel KW; Robidoux J; Czech MP; Mangelsdorf DJ; Collins S. 2008. Liver X receptor alpha is a transcriptional repressor of the uncoupling protein 1 gene and the brown fat phenotype. Mol Cell Biol 28(7):2187-200. [PubMed: 18195045]  [MGI Ref ID J:134191]

Watanabe M; Houten SM; Wang L; Moschetta A; Mangelsdorf DJ; Heyman RA; Moore DD; Auwerx J. 2004. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 113(10):1408-18. [PubMed: 15146238]  [MGI Ref ID J:120199]

Wu S; Yin R; Ernest R; Li Y; Zhelyabovska O; Luo J; Yang Y; Yang Q. 2009. Liver X receptors are negative regulators of cardiac hypertrophy via suppressing NF-kappaB signalling. Cardiovasc Res 84(1):119-26. [PubMed: 19487338]  [MGI Ref ID J:172488]

Zelcer N; Khanlou N; Clare R; Jiang Q; Reed-Geaghan EG; Landreth GE; Vinters HV; Tontonoz P. 2007. Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. Proc Natl Acad Sci U S A 104(25):10601-6. [PubMed: 17563384]  [MGI Ref ID J:122372]

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 & Husbandry

When maintained as a live colony, homozygotes or heterozygotes may be bred. The donating laboratory reports that breeders between the ages of 2 and 6 months of age show best productivity. They also recommend Teklad Global diets which are free of soybeans for experimental purposes. Soybeans are suspected of masking adrenal and neurodegenerative phenotypes associated with compound mutant strains that incorporate this Nr1h3 mutation (please review published literature). Our "Diet Information" link provides further details of the maintenance feed used at The Jackson Laboratory.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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Ordering Information
JAX^® Mice
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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Terms of Use

Terms of Use

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For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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General inquiries regarding Terms of Use

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phone:	207-288-6470
fax:	207-288-6655

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.

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.

No Liability

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.