Loss of PINK1 in medaka fish (Oryzias latipes) causes late-onset decrease in spontaneous movement
Loss of PINK1 in medaka fish (Oryzias latipes) causes late-onset decrease in spontaneous movement
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DOI：
10.1016/j.neures.2009.10.010
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Takahashi, Ryosuke
中科院分区：
文献类型：
--
作者：
Matsui, Hideaki;Taniguchi, Yoshihito;Takahashi, Ryosuke
帕金森病是一种与黑质多巴胺能神经元变性相关的神经退行性疾病。PTEN诱导的激酶1基因（PINK 1）是隐性遗传性家族性帕金森病（PARK 6）的致病基因。PINK 1的功能及其在预防帕金森病中的作用尚未完全了解。PINK 1的基因破坏在果蝇、斑马鱼和小鼠等动物模型中导致了显著不同的表型，其中没有一种重现帕金森病样症状。我们建立了PINK 1基因破坏的青鳉鱼。这些突变体鱼起初生长正常，但在成鱼后期自发游泳运动频率显著降低。虽然突变体没有表现出任何多巴胺能细胞的损失，但多巴胺的主要代谢产物3，4-二羟基苯乙酸的量。降低因此，PINK 1有助于维持多巴胺代谢，甚至在多巴胺能神经元选择性死亡之前。因此，我们的动物模型是一个有价值的工具，以检测帕金森病患者的发病机制在早期阶段。(C)2009年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
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. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.