STAGGERER PHENOTYPE IN RETINOID-RELATED ORPHAN RECEPTOR ALPHA-DEFICIENT MICE

Retinoid-related orphan receptor alpha (ROR alpha) is a member of the nuclear receptor superfamily, To study its physiological role we gener ated null-mutant mice by targeted insertion of a lacZ reporter gene en coding the enzyme beta-galactosidase. In heterozygous ROR alpha(+/-) m ice we found beta-galactosidase activity, indicative of ROR alpha prot ein expression, confined to the central nervous system, skin and testi s, In the central nervous system, the ROR alpha gene is expressed in c erebellar Purkinje cells, the thalamus, the suprachiasmatic nuclei, an d retinal ganglion cells, In skin, ROR alpha is strongly expressed in the hair follicle, the epidermis, and the sebacceous gland. Finally, t he peritubular cells of the testis and the epithelial cells of the epi didymis also strongly express ROR alpha, Recently, it was reported tha t tile ataxic mouse mutant staggerer (sg/sg) is caused by a deletion i n the ROR alpha gene, Tile analysis of the cerebellar and the behavior al phenotype of homozygous ROR alpha(-/-) mice proves identity to sg/s g mice, Although the absence of ROR alpha causes dramatic developmenta l effects in the cerebellum, it has no apparent morphological effect o n thalamus, hypothalamus, and retina, Similarly, testis and skin of RO R alpha(-/-) mice display a normal phenotype. However, the pelage hair of both sg/sg and ROR alpha(-/-) is significantly less dense and when shaved shows reluctance to regrow.