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Gene Review

Nr1h2  -  nuclear receptor subfamily 1, group H,...

Mus musculus

Synonyms: AI194859, LXR, LXRB, LXRbeta, Liver X receptor beta, ...
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Disease relevance of Nr1h2


Psychiatry related information on Nr1h2


High impact information on Nr1h2


Chemical compound and disease context of Nr1h2


Biological context of Nr1h2


Anatomical context of Nr1h2

  • Cholesterol-efflux studies verify that LXRbeta can drive apoA1-dependent cholesterol mobilization from macrophages [10].
  • Peroxisome proliferator-activated receptor (PPAR)alpha, PPARbeta/delta, and PPARgamma, liver X receptor (LXR)alpha and LXRbeta, farnesoid X receptor (FXR), and retinoid X receptor (RXR)alpha, RXRbeta, and RXRgamma mRNA levels were significantly decreased in the livers of 19-day pregnant mice [12].
  • We demonstrate here that the nuclear receptors LXRalpha and LXRbeta and their oxysterol ligands are key regulators of apoE expression in both macrophages and adipose tissue [13].
  • Most striking is the identification of one potential NFkappaB and seven potential Ets-protein binding sites in the LXRbeta promoter, suggesting an important role for this receptor in the haematopoietic/immune system [14].
  • The relative expression of, in particular, Lxrb was almost two orders of magnitude higher than in liver, brain and testis [15].

Associations of Nr1h2 with chemical compounds

  • Because the LXRs are important for cholesterol and lipid metabolism, we speculate that absence of LXRbeta leads to pathological accumulation of sterols and lipids that may themselves be neurotoxic or may modulate intracellular pathways and thereby predispose motor neurons to degeneration [8].
  • Our data lend further experimental support to the hypothesis that LXRbeta-selective agonists may raise HDL-cholesterol and stimulate macrophage cholesterol efflux without causing liver triglyceride accumulation [16].
  • This was accomplished by treating mice genetically deficient in either LXRalpha or LXRbeta with an agonist with equal potency for both isoforms (Compound B) or a synthetic agonist selective for LXRalpha (Compound A) [16].
  • Desmosterol bound to purified LXRalpha and LXRbeta in vitro and supported the recruitment of steroid receptor coactivator 1 [17].
  • Liver X receptors (LXRs), including LXRalpha and LXRbeta, are intracellular sterol sensors that regulate expression of genes controlling fatty acid and cholesterol absorption, excretion, catabolism, and cellular efflux [18].

Physical interactions of Nr1h2


Regulatory relationships of Nr1h2

  • We demonstrate here that the liver X receptors (LXRs) LXRalpha and LXRbeta inhibit basal and cytokine-inducible expression of MMP-9 [20].
  • Here we demonstrate that activation of liver X receptors (LXRs) LXRalpha and LXRbeta suppresses TF expression [21].

Other interactions of Nr1h2


Analytical, diagnostic and therapeutic context of Nr1h2


  1. Cross-talk between fatty acid and cholesterol metabolism mediated by liver X receptor-alpha. Tobin, K.A., Steineger, H.H., Alberti, S., Spydevold, O., Auwerx, J., Gustafsson, J.A., Nebb, H.I. Mol. Endocrinol. (2000) [Pubmed]
  2. Sterol regulatory element-binding protein 1 mediates liver X receptor-beta-induced increases in insulin secretion and insulin messenger ribonucleic acid levels. Zitzer, H., Wente, W., Brenner, M.B., Sewing, S., Buschard, K., Gromada, J., Efanov, A.M. Endocrinology (2006) [Pubmed]
  3. LXRbeta is required for adipocyte growth, glucose homeostasis, and beta cell function. Gerin, I., Dolinsky, V.W., Shackman, J.G., Kennedy, R.T., Chiang, S.H., Burant, C.F., Steffensen, K.R., Gustafsson, J.A., MacDougald, O.A. J. Biol. Chem. (2005) [Pubmed]
  4. Unr is required in vivo for efficient initiation of translation from the internal ribosome entry sites of both rhinovirus and poliovirus. Boussadia, O., Niepmann, M., Créancier, L., Prats, A.C., Dautry, F., Jacquemin-Sablon, H. J. Virol. (2003) [Pubmed]
  5. Placental expression of the nuclear receptors for oxysterols LXRalpha and LXRbeta during mouse and human development. Marceau, G., Volle, D.H., Gallot, D., Mangelsdorf, D.J., Sapin, V., Lobaccaro, J.M. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2005) [Pubmed]
  6. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Repa, J.J., Liang, G., Ou, J., Bashmakov, Y., Lobaccaro, J.M., Shimomura, I., Shan, B., Brown, M.S., Goldstein, J.L., Mangelsdorf, D.J. Genes Dev. (2000) [Pubmed]
  7. Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice. Alberti, S., Schuster, G., Parini, P., Feltkamp, D., Diczfalusy, U., Rudling, M., Angelin, B., Björkhem, I., Pettersson, S., Gustafsson, J.A. J. Clin. Invest. (2001) [Pubmed]
  8. Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice. Andersson, S., Gustafsson, N., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Role of nucleotide- and base-excision repair in genotoxin-induced neuronal cell death. Kisby, G.E., Lesselroth, H., Olivas, A., Samson, L., Gold, B., Tanaka, K., Turker, M.S. DNA Repair (Amst.) (2004) [Pubmed]
  10. Liver X Receptor (LXR)-beta Regulation in LXR{alpha}-Deficient Mice: Implications for Therapeutic Targeting. Quinet, E.M., Savio, D.A., Halpern, A.R., Chen, L., Schuster, G.U., Gustafsson, J.A., Basso, M.D., Nambi, P. Mol. Pharmacol. (2006) [Pubmed]
  11. Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism. Li, Y., Bolten, C., Bhat, B.G., Woodring-Dietz, J., Li, S., Prayaga, S.K., Xia, C., Lala, D.S. Mol. Endocrinol. (2002) [Pubmed]
  12. Decreased nuclear hormone receptor expression in the livers of mice in late pregnancy. Sweeney, T.R., Moser, A.H., Shigenaga, J.K., Grunfeld, C., Feingold, K.R. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  13. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Laffitte, B.A., Repa, J.J., Joseph, S.B., Wilpitz, D.C., Kast, H.R., Mangelsdorf, D.J., Tontonoz, P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  14. Structural characterisation of the mouse nuclear oxysterol receptor genes LXRalpha and LXRbeta. Alberti, S., Steffensen, K.R., Gustafsson, J.A. Gene (2000) [Pubmed]
  15. Reduced fertility and inability of oocytes to resume meiosis in mice deficient of the Lxr genes. Steffensen, K.R., Robertson, K., Gustafsson, J.A., Andersen, C.Y. Mol. Cell. Endocrinol. (2006) [Pubmed]
  16. 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. Lund, E.G., Peterson, L.B., Adams, A.D., Lam, M.H., Burton, C.A., Chin, J., Guo, Q., Huang, S., Latham, M., Lopez, J.C., Menke, J.G., Milot, D.P., Mitnaul, L.J., Rex-Rabe, S.E., Rosa, R.L., Tian, J.Y., Wright, S.D., Sparrow, C.P. Biochem. Pharmacol. (2006) [Pubmed]
  17. Sterol intermediates from cholesterol biosynthetic pathway as liver x receptor ligands. Yang, C., McDonald, J.G., Patel, A., Zhang, Y., Umetani, M., Xu, F., Westover, E.J., Covey, D.F., Mangelsdorf, D.J., Cohen, J.C., Hobbs, H.H. J. Biol. Chem. (2006) [Pubmed]
  18. Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule. Zhang, Y., Zhang, X., Chen, L., Wu, J., Su, D., Lu, W.J., Hwang, M.T., Yang, G., Li, S., Wei, M., Davis, L., Breyer, M.D., Guan, Y. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  19. Oxysterol-activated LXRalpha/RXR induces hSR-BI-promoter activity in hepatoma cells and preadipocytes. Malerød, L., Juvet, L.K., Hanssen-Bauer, A., Eskild, W., Berg, T. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  20. Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. Castrillo, A., Joseph, S.B., Marathe, C., Mangelsdorf, D.J., Tontonoz, P. J. Biol. Chem. (2003) [Pubmed]
  21. Liver X receptor agonists inhibit tissue factor expression in macrophages. Terasaka, N., Hiroshima, A., Ariga, A., Honzumi, S., Koieyama, T., Inaba, T., Fujiwara, T. FEBS J. (2005) [Pubmed]
  22. Overlapping transcriptional programs regulated by the nuclear receptors peroxisome proliferator-activated receptor alpha, retinoid X receptor, and liver X receptor in mouse liver. Anderson, S.P., Dunn, C., Laughter, A., Yoon, L., Swanson, C., Stulnig, T.M., Steffensen, K.R., Chandraratna, R.A., Gustafsson, J.A., Corton, J.C. Mol. Pharmacol. (2004) [Pubmed]
  23. Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity. Dahlman, I., Nilsson, M., Jiao, H., Hoffstedt, J., Lindgren, C.M., Humphreys, K., Kere, J., Gustafsson, J.A., Arner, P., Dahlman-Wright, K. Pharmacogenet. Genomics (2006) [Pubmed]
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