Chorein deficiency leads to upregulation of gephyrin and GABA(A) receptor |
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Authors: | Kurano Yutaka Nakamura Masayuki Ichiba Mio Matsuda Mieko Mizuno Emiko Kato Maiko Izumo Shuji Sano Akira |
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Institution: | Department of Psychiatry, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan. |
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Abstract: | 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 alpha1 (GABRA1) and gamma2 (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. |
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Keywords: | Chorein Chorea-acanthocytosis VPS13A Gephyrin GABAA receptor Neurodegeneration |
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