Chorein deficiency leads to upregulation of gephyrin and GABA_A receptor

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• 作者：Yutaka Kurano ; Masayuki Nakamura ; Mio Ichiba ; Mieko Matsuda ; Emiko Mizuno ; Maiko Kato ; Shuji Izumo ; Akira Sano
• 关键词：Chorein ; Chorea-acanthocytosis ; VPS13A ; Gephyrin ; GABA_A receptor ; Neurodegeneration
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：15 December 2006
• 卷：351
• 期：2
• 页码：438-442
• 文件大小：514 K

摘要

Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by loss of function mutations in the VPS13A gene encoding chorein. Recently, using a gene-targeting technique to delete exons 60–61, we produced a ChAc-model mouse that corresponds to a human disease mutation. In this study, a comparative microarray analysis of gene expression in the striatum revealed an increased level of gephyrin gene expression in the ChAc-model mice compared with wild type mice. Since gephyrin is known as a GABA_A receptor-anchoring protein, we compared the protein-level expression and localization of gephyrin and the GABA_A receptor α1 (GABRA1) and γ2 (GABRG2) subunits. Gephyrin and GABRG2 immunoreactivities in the striatum and hippocampus of the ChAc-model mice were significantly higher than those in the wild types. Our results suggest that chorein functional loss may lead to a compensatory upregulation of gephyrin and GABRG2 in the pathologic condition in ChAc.