Loss of PINK1 in medaka fish (Oryzias latipes) causes late-onset decrease in spontaneous movement

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• 作者：Hideaki Matsui ; Yoshihito Taniguchi ; Haruhisa Inoue ; Yoshito Kobayashi ; Yoshiyuki Sakaki ; Atsushi Toyoda ; Kengo Uemura ; Daisuke Kobayashi ; Shunichi Takeda ; Ryosuke Takahashi
• 关键词：Parkinson's disease ; PTEN-induced kinase 1 (PINK1) ; Medaka fish (Oryzias latipes) ; TILLING (targeted induced local lesions in genomes) ; Dopamine ; Movement disorder
• 刊名：Neuroscience Research
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：66
• 期：2
• 页码：151-161
• 全文大小：2178 K

文摘

Parkinson's disease is a neurodegenerative disease associated with the degeneration of dopaminergic neurons in the substantia nigra. The PTEN-induced kinase 1 gene (PINK1) is responsible for recessive inherited familial Parkinson's disease (PARK6). Neither the function of PINK1 nor its role in the prevention of Parkinson's disease is fully understood. Gene disruption of PINK1 causes remarkably different phenotypes in animal models such as Drosophila melanogaster, zebrafish, and mouse, none of which recapitulate Parkinson's-disease-like symptoms. We established PINK1-gene-disrupted medaka fish. These mutant fish grew normally at first, then developed significant decrease in the frequency of spontaneous swimming movements in the late-adult stage. Although the mutants did not show any dopaminergic cell loss, the amount of 3,4-dihydroxyphenylacetic acid, a major metabolite of dopamine, decreased. Thus, PINK1 contributes to the maintenance of dopamine metabolism, even before the selective death of dopaminergic neurons. Our animal model is therefore a valuable tool to detect pathogenesis in Parkinson's patients in the early stages.