Research Grant Award

Andrea Richter, PhD

Hopital Sainte-Justine
New tools to study autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS)

We are investigating ARSACS. a clinically well studied form of inherited ataxia that is frequent in Quebec but has now been recognized in several other countries. Our previous efforts yielded the chromosomal localization of the disease gene and the identification of disease mutations in the SACS gene in Quebec and Turkish patients.

The function of the product coded by the SACS gene, sacsin is unknown. It is a large protein with a predicted molecular weight of over 500 kDaltons. We are currently generating the tools required to study protein function. These include the creation of animal models of the disease and the production of a panel of antibodies to study the cell biology of sacsin. We are also investigating the interaction partners of sacsin since their identification could lead to the understanding of protein function.

Using previous funding from the NAF we produced the targeting vectors required to create the SACS knock-out mice. The steps (targeting of ES cells, clone selection, blastocyst injections) leading to chimeric mice are currently underway using funding from other sources.

Using fragments of sacsin expressed in a bacterial system we created 2 antibodies that are able to detect sacsin under in vitro conditions but are not specific enough to be used for other studies.

The current proposal aims to increase the number and specificity of anti-sacsin antibodies and to undertake the cloning steps needed to identify the interaction partners.