DRPLA遺伝子の生理的機能解明に向けたノックアウトマウスの作成
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概要
- 論文の詳細を見る
DRPLA is an autosomal, dominantly inherited neurodegenerative disorder that is characterized by various combinations of symptoms including ataxia, choreoathetosis, myoclonus, epilepsy, dementia and psychiatric symptoms and selective neuronal loss including dentate nucleus, red nucleus, globus pallidus and subthalamic nucleus. In patients with DRPLA, the CAG trinucleotide repeat in exon 5 of DRPLA gene coding for polyglutamine stretches is expanded to a length exceeding 49 repeat units. It has been demonstrated that there is an inverse correlation between the size of expanded CAG repeats and the age at onset. The physiological functions of the gene products of the causative genes for polyglutamine diseases, however, remain to be determined, except for the androgen receptor (SBMA) and the α 1A voltage-depended calcium channel (SCA6). To gain insight into the physiological roles of the wild-type DRPLA protein, a widely expressed protein with no known homologies to any of the proteins, we generated mice with a targeted disruption of the DRPLA gene. The mutant mice grow into adulthood although mice heterozygous and homozygous for this mutation displayed neurological phenotypes including involuntary movements. These results suggest that DRPLA protein has physiological functions essential for the central nervous system, and, furthermore, that even half dose of wild-type of DRPLA gene results in phenotypic expression. The present mice should be highly useful for investigating physiological functions of DRPLA protein.
- 新潟大学の論文
- 2002-06-10