2006/06/29 by Mohamed Doulazmi, Doulazmi, Mohamed, Francesca Capone +10
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Amyotrophic Lateral Sclerosis Research #FOS: Biological sciences #Genetic Neurodegenerative Diseases #Neurons and Cognition (q-bio.NC) #RNA regulation and disease
paper · pdf · doi:10.48550/arxiv.q-bio/0606040
openalex publication_date 2006/06/29 · openalex created_date 2022/11/05 · openalex updated_date 2026/07/28
The staggerer (sg/sg) mutation is a spontaneous deletion in the Rora gene\nthat prevents the translation of the ligand-binding domain (LBD), leading to\nthe loss of ROR\α activity. The homozygous Rorasg/sg mutant mouse, whose\nmost obvious phenotype is ataxia associated with cerebellar degeneration, also\ndisplays a variety of other phenotypes. The heterozygous Rora+/sg is able to\ndevelop a cerebellum which is qualitatively normal but with advancing age\nsuffers a significant loss of cerebellar neuronal cells. A truncated protein\nsynthesized by the mutated allele may play a role, both in Rorasg/sg and\nRora+/sg. To determine the effects during life span of true haplo-insufficiency\nof the ROR\α protein, derived from the invalidation of the gene, we\ncompared the evolution of Purkinje cell numbers in heterozygous Rora knock-out\nmales (Rora+/-) and in their wildtype counterparts from 1 to 24 months of age.\nWe also compared the evolution of Purkinje cell numbers in Rora+/- and Rora+/sg\nmales from 1 to 9 months. The main finding is that in Rora+/- mice, when only a\nhalf dose of protein is synthesized, the deficit was already established at 1\nmonth and did not change during life span....\n