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  • Title: A comparative study of Purkinje cells in two RORalpha gene mutant mice: staggerer and RORalpha(-/-).
    Author: Doulazmi M, Frédéric F, Capone F, Becker-André M, Delhaye-Bouchaud N, Mariani J.
    Journal: Brain Res Dev Brain Res; 2001 Apr 30; 127(2):165-74. PubMed ID: 11335003.
    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.
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