Publication in detail

Mol Brain. 2019 Mar 12;12(1):19. doi: 10.1186/s13041-019-0438-3.

Sacs R272C missense homozygous mice develop an ataxia phenotype.

Larivière, R; Sgarioto, N; Márquez, BT; Gaudet, R; Choquet, K; McKinney, RA; Watt, AJ; Brais, B

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Room 622, 3801, University Street, Montreal, Québec, H3A 2B4, Canada. Department of Biology, McGill University, Montreal, Qc, Canada. Department of Human Genetics, Montreal Neurological Institute, McGill University, Montreal, Qc, Canada. Department of Pharmacology and Therapeutics, McGill University, Montreal, Qc, Canada. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Room 622, 3801, University Street, Montreal, Québec, H3A 2B4, Canada.

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 SacsR272C mice express 21% of wild type brain sacsin and sacsin is found in many neurons, they display similar abnormalities to Sacs knock-out mice, including the development of an ataxic phenotype, reduced Purkinje cell firing rates, and somatodendritic neurofilament bundles in Purkinje cells and other neurons. Together our results support that Sacs missense mutation largely lead to loss of sacsin function.

» Online Version

Proven Track Record

The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.

Go to Publications

Global Client Base

Ozgene generates genetically customised mice for researchers around the world. Ozgene mice can be found in 31 different countries on 5 continents from small academic institutions to multinational pharmaceutical companies.

See Map

Lean Management

Ozgene is applying Lean Management principles to deliver the highest quality services and shortest lead times to our customers. The implementation of Lean Culture has already seen an improvement in our processes and timelines.

Read More