Loss of PINK1 in medaka fish (Oryzias latipes) causes late-onset decrease in spontaneous movement.
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.
Matsui
Hideaki
H
Department of Neurology, Kyoto University, Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Taniguchi
Yoshihito
Y
Inoue
Haruhisa
H
Kobayashi
Yoshito
Y
Sakaki
Yoshiyuki
Y
Toyoda
Atsushi
A
Uemura
Kengo
K
Kobayashi
Daisuke
D
Takeda
Shunichi
S
Takahashi
Ryosuke
R
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D046529:Microscopy, Electron, Transmission; D009068:Movement / Q000502:physiology*; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009990:Oryzias; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D013550:Swimming / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D029941:Fish Proteins; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D011494:Protein Kinases; D004298:Dopamine