Mutant β-III spectrin causes mGluR1α mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5.

ABSTRACT: Spinocerebellar ataxia type 5 (SCA5), a dominant neurodegenerative disease characterized by profound Purkinje cell loss, is caused by mutations in SPTBN2, a gene that encodes β-III spectrin. SCA5 is the first neurodegenerative disorder reported to be caused by mutations in a cytoskeletal spectrin gene. We have developed a mouse model to understand the mechanistic basis for this disease and show that expression of mutant but not wild-type β-III spectrin causes progressive motor deficits and cerebellar degeneration. We show that endogenous β-III spectrin interacts with the metabotropic glutamate receptor 1α (mGluR1α) and that mice expressing mutant β-III spectrin have cerebellar dysfunction with altered mGluR1α localization at Purkinje cell dendritic spines, decreased mGluR1-mediated respons

SUBMITTER: Armbrust KR 

PROVIDER: S-EPMC4107406 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature