The role of capicua in spinocerebellar ataxia type 1

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The goal of this project is to determine the role of capicua (Cic) in spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease caused by a polyglutamine expansion in Ataxin-1 (Atx-1). Cic is a transcriptional represser in Drosophila and preliminary results show that Cic interacts with Atx-1, co-localizes to Purkinje neurons that degenerate in SCA1, and its level is reduced in Atx-1-null mice. I will first analyze the expression of Cic during development in wild-type and Atx-1-null mice. I will generate and characterize Cic- null mice (Cic-/-) to determine the normal role of Cic in vivo and to determine its role in the normal function of Atx-1 (when crossed to Atx-1-null mice). Cic-null mice will be crossed to a knock-in model of SCA1 to determine whether and how Cic affects SCA1 pathogenesis. Given Cic's role as a transcriptional represser, I will investigate gene expression changes by microarray analysis in Cic and Cic-/- mice. Changes in Cic mutants will be compared to those of Atx-1-null and SCA1 knock-in mice (currently being performed by other laboratory members) to pinpoint those changes most relevant to SCA1 and Atx-1 function. This project will establish the role of Cic in mammals and in the normal function of Atx-1 and in SCA1 pathogenesis.