title: A comparative study of Purkinje cells in two RORalpha gene mutant mice: staggerer and RORalpha(-/-).
abstract: The staggerer (Rora(sg/sg)) mutation is a deletion in the RORalpha gene, one member of a family of nuclear receptor genes related to the retinoic acid receptor. Recently Steinmayr et al. (Proc. Natl. Acad. Sci. USA 95 (1998) 3960) generated a RORalpha null-mutant mouse (Rora(-/-)) by using a targeting vector in which a beta-Gal gene replaces the second finger of the DNA-binding domain of RORalpha. The Rora(-/-) cerebellum is qualitatively a phenocopy of the Rora(sg/sg) one, but the two strains differ slightly in their motor skills. To address the question whether the morphological defects in the Rora(-/-) cerebellum are identical to the Rora(sg/sg) one, we compared number and size of Purkinje cells in both staggerer and RORalpha null-mutant mice, using calbindin (CaBP) immunohistochemistry and revelation of beta-Gal activity. Compared to control cerebella the Rora(sg/sg) cerebellum has 82% fewer CaBP-positive cells. In Rora(-/-) mouse, all the the beta-Gal-positive Purkinje cells also expressed CaBP, but the cerebellum contained 78% less CaBP-positive cells than control, a deficit not different from the one observed in Rora(sg/sg). We show similar mediolateral compartments in Purkinje cell number and cytological abnormality in Rora(sg/sg) and Rora(-/-) mice. These results provide quantitative support for the hypothesis that the cerebellar phenotype in the homozygous Rora(sg/sg) is due to the lack of function of the RORalpha gene.
authors.affiliation: Laboratoire Développement et Vieillissement du Système Nerveux, Institut des Neurosciences UMR 7624 CNRS, Université P. and M. Curie, 75005, Paris, France. mohamed.doulazmi@snv.jussieu.fr
authors.forename: M
authors.initials: M
authors.lastname: Doulazmi
authors.forename: F
authors.initials: F
authors.lastname: Frédéric
authors.forename: F
authors.initials: F
authors.lastname: Capone
authors.forename: M
authors.initials: M
authors.lastname: Becker-André
authors.forename: N
authors.initials: N
authors.lastname: Delhaye-Bouchaud
authors.forename: J
authors.initials: J
authors.lastname: Mariani
mesh_terms: D000818:Animals; D048429:Cell Size; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D010641:Phenotype; D011689:Purkinje Cells / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; C539739:Rora protein, mouse; D015534:Trans-Activators