The role of capicua in spinocerebellar ataxia type 1

Capicua 在 1 型脊髓小脑共济失调中的作用

• 批准号: 7113397
• 负责人: John David Fryer
• 金额: $ 4.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113397
• 关键词: Drosophilidae; ataxia; homopeptide; phenotype; proteins; role

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.

描述（由申请人提供）：本项目的目标是确定capicua （Cic）在脊髓小脑性共济失调1型（SCA1）中的作用，SCA1是一种由Ataxin-1 （Atx-1）中聚谷氨酰胺扩增引起的神经退行性疾病。Cic在果蝇中是一种转录抑制因子，初步结果表明Cic与Atx-1相互作用，共定位于SCA1中退化的浦肯野神经元，并且在Atx-1缺失的小鼠中其水平降低。我将首先分析Cic在野生型和atx -1缺失小鼠发育过程中的表达。我将生成并表征Cic- null小鼠（Cic-/-），以确定Cic在体内的正常作用，并确定其在Atx-1正常功能中的作用（当与Atx-1-null小鼠杂交时）。将Cic缺失的小鼠与SCA1敲入模型杂交，以确定Cic是否以及如何影响SCA1的发病机制。鉴于Cic作为转录抑制因子的作用，我将通过微阵列分析在Cic和Cic-/-小鼠中研究基因表达的变化。Cic突变体的变化将与Atx-1缺失和SCA1敲入小鼠的变化进行比较（目前由其他实验室成员进行），以确定与SCA1和Atx-1功能最相关的变化。本项目将确定Cic在哺乳动物中的作用，以及在Atx-1的正常功能和SCA1发病机制中的作用。