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Rora  -  RAR-related orphan receptor alpha

Mus musculus

Synonyms: 9530021D13Rik, Nr1f1, Nuclear receptor ROR-alpha, Nuclear receptor RZR-alpha, Nuclear receptor subfamily 1 group F member 1, ...
 
 
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Disease relevance of Rora

 

Psychiatry related information on Rora

 

High impact information on Rora

  • The recent identification of ROR2, encoding an orphan receptor tyrosine kinase, as the gene mutated in brachydactyly type B (BDB1; ref. 7) and the mesomelic dwarfing in mice homozygous for a lacZ and/or a neo insertion into Ror2 (refs 8,9) made this gene a candidate for RRS [11].
  • In addition, sg heterozygotes show accelerated dendritic atrophy and cell loss, suggesting that sg has a role in mature Purkinje cells [12].
  • Homozygous staggerer (sg) mice show a characteristic severe cerebellar ataxia due to a cell-autonomous defect in the development of Purkinje cells [12].
  • We have genetically mapped staggerer to an interval of 160 kilobases on mouse chromosome 9 which was found to contain the gene encoding RORalpha, a member of the nuclear hormone-receptor superfamily [12].
  • These results demonstrate that the amino-terminal domain and the zinc finger region work in concert to confer high affinity and specific DNA-binding properties to the ROR isoforms and suggest a novel strategy to control DNA-binding activity of nuclear receptors [13].
 

Chemical compound and disease context of Rora

 

Biological context of Rora

  • A functional genomics strategy reveals Rora as a component of the mammalian circadian clock [6].
  • Using interspecific backcross analysis, we have mapped the Rora gene to mouse chromosome 9 [15].
  • Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice [16].
  • These findings suggest that there is a distinct mediolateral heterogeneity in the staggerer cerebellum with respect to transcription levels of these Purkinje cell-specific molecules, which might correlate with some cytological phenotypes [17].
  • Our data suggest that the sg/sg mutation does not interfere with the transcriptional activation of these two genes, and might therefore act after the induction of specific gene expression in developing Purkinje cells [18].
 

Anatomical context of Rora

  • There was also some delay in E leads to A conversion within the cerebral cortex of sg/sg, although phenotypically no evidence of cortical disorder has been detected [16].
  • In both reeler and weaver mutant mice in the adult stage, all Purkinje cells were positive for c-fms as in the wild-type controls; however, the parasagittal bands of c-fms-positive Purkinje cells were observed even in the adult staggerer mutant [19].
  • The Purkinje cells in the staggerer mutant mouse have various cellular abnormalities, including reduced cell number, ectopia, smaller size and absence of dendritic spines [17].
  • The recessive mouse mutation staggerer (sg) disturbs the normal development of cerebellar Purkinje cells and affects certain functions of the immune system [20].
  • Substantially lower [3H]flunitrazepam labeling was detected over the cerebellar cortex of 25-27-day-old sg/sg mutants in which the number of granule, Purkinje and Golgi cells is greatly reduced; the labeling over the deep nuclei, however, was significantly increased [21].
 

Associations of Rora with chemical compounds

 

Regulatory relationships of Rora

 

Other interactions of Rora

  • This result suggests an additional linkage between Ncam and the locus for the cerebellar mutation staggerer (sg) [27].
  • In staggerer mice, neurons immunopositive for Parv as well as for Calb were present in outer DCN areas, likely representing ectopic PCs rather than DCN neurons [28].
  • In the cerebella of two neurological granule cell-deficient mutants, weaver (wv) and staggerer (sg), parallin is not detected [29].
  • Using cell-based functional assays, as well as behavioral and molecular analyses, we identified Rora as an activator of Bmal1 transcription within the SCN [6].
  • CONCLUSION: That the Pcp-2 gene is a target of ROR alpha, and is suggested that its transcription is also regulated by RAR [23].
 

Analytical, diagnostic and therapeutic context of Rora

References

  1. RORalpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR. Lau, P., Nixon, S.J., Parton, R.G., Muscat, G.E. J. Biol. Chem. (2004) [Pubmed]
  2. Retinoic acid receptor-related orphan receptor (ROR) alpha4 is the predominant isoform of the nuclear receptor RORalpha in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cells. Chauvet, C., Bois-Joyeux, B., Danan, J.L. Biochem. J. (2002) [Pubmed]
  3. Cellular distribution of gangliosides in the developing mouse cerebellum: analysis using the staggerer mutant. Seyfried, T.N., Bernard, D.J., Yu, R.K. J. Neurochem. (1984) [Pubmed]
  4. Glutamate dehydrogenase in cerebellar mutant mice: gene localization and enzyme activity in different tissues. Miret-Duvaux, O., Frederic, F., Simon, D., Guenet, J.L., Hanauer, A., Delhaye-Bouchaud, N., Mariani, J. J. Neurochem. (1990) [Pubmed]
  5. Enhanced susceptibility of staggerer (RORalphasg/sg) mice to lipopolysaccharide-induced lung inflammation. Stapleton, C.M., Jaradat, M., Dixon, D., Kang, H.S., Kim, S.C., Liao, G., Carey, M.A., Cristiano, J., Moorman, M.P., Jetten, A.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  6. A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Sato, T.K., Panda, S., Miraglia, L.J., Reyes, T.M., Rudic, R.D., McNamara, P., Naik, K.A., FitzGerald, G.A., Kay, S.A., Hogenesch, J.B. Neuron (2004) [Pubmed]
  7. A comparative study of Purkinje cells in two RORalpha gene mutant mice: staggerer and RORalpha(-/-). Doulazmi, M., Frédéric, F., Capone, F., Becker-André, M., Delhaye-Bouchaud, N., Mariani, J. Brain Res. Dev. Brain Res. (2001) [Pubmed]
  8. Restoration of staggerer mouse maternal behavior following long-term breeding selection. Boufares, S., Guastavino, J.M., Larsson, K. Physiol. Behav. (1993) [Pubmed]
  9. Effects of the rearing temperature on the temporal feeding pattern of the staggerer mutant mouse. Guastavino, J.M., Bertin, R., Portet, R. Physiol. Behav. (1991) [Pubmed]
  10. Exploration and spatial learning in staggerer mutant mice. Lalonde, R. J. Neurogenet. (1987) [Pubmed]
  11. Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2. Afzal, A.R., Rajab, A., Fenske, C.D., Oldridge, M., Elanko, N., Ternes-Pereira, E., Tüysüz, B., Murday, V.A., Patton, M.A., Wilkie, A.O., Jeffery, S. Nat. Genet. (2000) [Pubmed]
  12. Disruption of the nuclear hormone receptor RORalpha in staggerer mice. Hamilton, B.A., Frankel, W.N., Kerrebrock, A.W., Hawkins, T.L., FitzHugh, W., Kusumi, K., Russell, L.B., Mueller, K.L., van Berkel, V., Birren, B.W., Kruglyak, L., Lander, E.S. Nature (1996) [Pubmed]
  13. Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Giguère, V., Tini, M., Flock, G., Ong, E., Evans, R.M., Otulakowski, G. Genes Dev. (1994) [Pubmed]
  14. Melatonin and RZR/ROR receptor ligand CGP 52608 induce apoptosis in the murine colonic cancer. Winczyk, K., Pawlikowski, M., Karasek, M. J. Pineal Res. (2001) [Pubmed]
  15. The orphan nuclear receptor ROR alpha (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9. Giguère, V., Beatty, B., Squire, J., Copeland, N.G., Jenkins, N.A. Genomics (1995) [Pubmed]
  16. Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Edelman, G.M., Chuong, C.M. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  17. Regional variation in expression of calbindin and inositol 1,4,5-trisphosphate receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse. Nakagawa, S., Watanabe, M., Inoue, Y. Eur. J. Neurosci. (1996) [Pubmed]
  18. Presence of calbindin D28K and GAD67 mRNAs in both orthotopic and ectopic Purkinje cells of staggerer mice suggests that staggerer acts after the onset of cytodifferentiation. Frantz, G.D., Wuenschell, C.W., Messer, A., Tobin, A.J. J. Neurosci. Res. (1996) [Pubmed]
  19. Expression pattern and neurotrophic role of the c-fms proto-oncogene M-CSF receptor in rodent Purkinje cells. Murase, S., Hayashi, Y. J. Neurosci. (1998) [Pubmed]
  20. The structural integrity of ROR alpha isoforms is mutated in staggerer mice: cerebellar coexpression of ROR alpha1 and ROR alpha4. Matysiak-Scholze, U., Nehls, M. Genomics (1997) [Pubmed]
  21. Cerebellar benzodiazepine receptors: cellular localization and consequences of neurological mutations in mice. Rotter, A., Frostholm, A. Brain Res. (1988) [Pubmed]
  22. ROR alpha gene expression in the perinatal rat cerebellum: ontogeny and thyroid hormone regulation. Koibuchi, N., Chin, W.W. Endocrinology (1998) [Pubmed]
  23. Transcriptional regulation of a Purkinje cell-specific gene through a functional interaction between ROR alpha and RAR. Matsui, T. Genes Cells (1997) [Pubmed]
  24. Developmental expression and intracellular location of P400 protein characteristic of Purkinje cells in the mouse cerebellum. Maeda, N., Niinobe, M., Inoue, Y., Mikoshiba, K. Dev. Biol. (1989) [Pubmed]
  25. Differential IL-6 mRNA expression by stimulated peripheral macrophages of Staggerer and Lurcher cerebellar mutant mice. Kopmels, B., Mariani, J., Taupin, V., Delhaye-Bouchaud, N., Wollman, E.E. Eur. Cytokine Netw. (1991) [Pubmed]
  26. Social isolation induces preference for odours of oestrous females in sexually naive male staggerer mutant mice. Féron, C., Baudoin, C. Chem. Senses (1998) [Pubmed]
  27. Chromosomal location of the gene encoding the neural cell adhesion molecule (N-CAM) in the mouse. D'Eustachio, P., Owens, G.C., Edelman, G.M., Cunningham, B.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  28. Dependence of parvalbumin expression on Purkinje cell input in the deep cerebellar nuclei. Bäurle, J., Hoshi, M., Grüsser-Cornehls, U. J. Comp. Neurol. (1998) [Pubmed]
  29. Parallin, a cerebellar granule cell protein the expression of which is developmentally regulated by Purkinje cells: evidence from mutant mice. Smith, A.M., Mullen, R.J. Brain Res. Dev. Brain Res. (1997) [Pubmed]
  30. Interleukin-1 hyperproduction by in vitro activated peripheral macrophages from cerebellar mutant mice. Kopmels, B., Wollman, E.E., Guastavino, J.M., Delhaye-Bouchaud, N., Fradelizi, D., Mariani, J. J. Neurochem. (1990) [Pubmed]
  31. Cytological compartmentalization in the staggerer cerebellum, as revealed by calbindin immunohistochemistry for Purkinje cells. Nakagawa, S., Watanabe, M., Isobe, T., Kondo, H., Inoue, Y. J. Comp. Neurol. (1998) [Pubmed]
  32. Intranuclear relocation of the Plc beta3 sequence in cerebellar purkinje neurons: temporal association with de novo expression during development. Martou, G., Park, P.C., De Boni, U. Chromosoma (2002) [Pubmed]
  33. Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha. Mamontova, A., Séguret-Macé, S., Esposito, B., Chaniale, C., Bouly, M., Delhaye-Bouchaud, N., Luc, G., Staels, B., Duverger, N., Mariani, J., Tedgui, A. Circulation (1998) [Pubmed]
 
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