Staggerer Phenotype in Retinoid-Related Orphan Receptor α -Deficient Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 7; pp. 3960 - 3965
• Main Authors: Steinmayr, Markus, Andre, Elisabeth, Conquet, Francois, Rondi-Reig, Laure, Delhaye-Bouchaud, Nicole, Auclair, Nathalie, Daniel, Herve, Crepel, Francis, Mariani, Jean, Sotelo, Constantino, Becker-Andre, Michael
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 31.03.1998; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Animals; Behavior, Animal - physiology; Biological Sciences; Cerebellum; Cerebellum - physiology; Dendrites; Enzymes; Epithelial cells; Gene Expression Regulation; Genes; Genetic mutation; Mice; Mice, Mutant Strains; Mutation; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Neurology; Nuclear Receptor Subfamily 1, Group F, Member 1; Organ Specificity; Phenotypes; Purkinje cells; Receptors, Cytoplasmic and Nuclear - deficiency; Receptors, Cytoplasmic and Nuclear - genetics; Rodents; Skin; Testes; Trans-Activators - deficiency; Trans-Activators - genetics; Zinc
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.7.3960

Retinoid-related orphan receptor α (RORα ) is a member of the nuclear receptor superfamily. To study its physiological role we generated null-mutant mice by targeted insertion of a lacZ reporter gene encoding the enzyme β -galactosidase. In heterozygous RORα+/-mice we found β -galactosidase activity, indicative of RORα protein expression, confined to the central nervous system, skin and testis. In the central nervous system, the RORα gene is expressed in cerebellar Purkinje cells, the thalamus, the suprachiasmatic nuclei, and retinal ganglion cells. In skin, RORα is strongly expressed in the hair follicle, the epidermis, and the sebaceous gland. Finally, the peritubular cells of the testis and the epithelial cells of the epididymis also strongly express RORα . Recently, it was reported that the ataxic mouse mutant staggerer (sg/sg) is caused by a deletion in the RORα gene. The analysis of the cerebellar and the behavioral phenotype of homozygous RORα-/-mice proves identity to sg/sg mice. Although the absence of RORα causes dramatic developmental effects in the cerebellum, it has no apparent morphological effect on thalamus, hypothalamus, and retina. Similarly, testis and skin of RORα-/-mice display a normal phenotype. However, the pelage hair of both sg/sg and RORα-/-is significantly less dense and when shaved shows reluctance to regrow.