RRC ID 12312
著者 Matsui H, Taniguchi Y, Inoue H, Kobayashi Y, Sakaki Y, Toyoda A, Uemura K, Kobayashi D, Takeda S, Takahashi R.
タイトル Loss of PINK1 in medaka fish (Oryzias latipes) causes late-onset decrease in spontaneous movement.
ジャーナル Neurosci Res
Abstract 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.
巻・号 66(2)
ページ 151-61
公開日 2010-2-1
DOI 10.1016/j.neures.2009.10.010
PII S0168-0102(09)02015-X
PMID 19895857
MeSH Age Factors Analysis of Variance Animals Animals, Genetically Modified Behavior, Animal / physiology* Blotting, Western Body Weight / genetics Brain / metabolism* Chromatography, High Pressure Liquid Dopamine / metabolism Fish Proteins / genetics Fish Proteins / metabolism Immunohistochemistry In Situ Hybridization Microscopy, Electron, Transmission Movement / physiology* Mutation Neurons / metabolism* Oryzias Protein Kinases / genetics* Protein Kinases / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Staining and Labeling Swimming / physiology Ubiquitin-Protein Ligases / metabolism
IF 2.645
引用数 20
WOS 分野 NEUROSCIENCES
リソース情報
メダカ TILLING_MUTANT