Age-related phenotypes in the staggerer mouse expand the RORα nuclear receptor's role beyond the cerebellum

被引:57
作者
Jarvis, CI
Staels, B
Brugg, B
Lemaigre-Dubreuil, Y
Tedgui, A
Mariani, J
机构
[1] Univ Paris 06, F-75005 Paris, France
[2] CNRS, FRE 2371 Neurobiol Proc Adaptatifs, F-75005 Paris, France
[3] Univ Lille 2, Fac Pharm, Inst Pasteur Lille, UR545 INSERM, F-59019 Lille, France
[4] Hop Lariboisiere, U541 INSERM, F-75475 Paris, France
关键词
Purkinje cells; osteoporosis; atherosclerosis; NF-kappa B; Rev-erb; CaM kinase;
D O I
10.1016/S0303-7207(01)00668-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The homozygous mutant mouse staggerer (RORasg /RORasg), was initially described as ataxic, due to the presence of massive neuro degeneration in the cerebellum [Science 136 (1962) 610]. The identification of the widely expressed Retinoic acid receptor-related Orphan Receptor, NRIFI (RORalpha) gene as the site of mutation in the staggerer mouse has led to great progress in understanding the molecular basis of its phenotype in recent years [Nature 379 (1996) 736]. RORalpha is a transcription factor, belonging to the nuclear receptor superfamily, for which no natural ligand has yet been identified. Mice engineered for the disruption of the gene encoding RORalpha display the same cerebellar atrophic phenotype as the staggerer mouse [Proc. Natl. Acad. Sci. USA 95 (1998) 3960]. More recently, it has been shown that the mutation is semi-dominant, as heterozygous animals display an increased loss of Purkinje cells with age. Furthermore, a number of additional phenotypes outside the nervous system have recently been identified. These include a greater susceptibility to atherosclerosis [Circulation 15 (1998) 2738], immunodeficiencies linked to the overexpression of inflammatory cytokines [J. Neurochem. 58 (1992) 192], abnormalities in the formation and maintenance of bone tissue [Proc. Natl. Acad. Sci. USA 97 (2000) 9197] and changes in muscle differentiation [Nucleic Acids Res. 27 (1999) 411]. Thus, RORalpha has been directly linked to a number of age-related pathologies of great medical interest. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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页码:1 / 5
页数:5
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