Sacs R272C missense homozygous mice develop an ataxia phenotype.

ABSTRACT: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS [MIM 270550]) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. Over 200 SACS mutations have been identified. Most mutations lead to a complete loss of a sacsin, a large 520 kD protein, although some missense mutations are associated with low levels of sacsin expression. We previously showed that Sacs knock-out mice demonstrate early-onset ataxic phenotype with neurofilament bundling in many neuronal populations. To determine if the preservation of some mutated sacsin protein resulted in the same cellular and behavioral alterations, we generated mice expressing an R272C missense mutation, a homozygote mutation found in some affected patients. Though Sacs^R272C mice express 21% of wi

SUBMITTER: Lariviere R 

PROVIDER: S-EPMC6416858 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature