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dc.contributor.authorUemura, Norihitoja
dc.contributor.authorKoike, Masatoja
dc.contributor.authorAnsai, Satoshija
dc.contributor.authorKinoshita, Masatoja
dc.contributor.authorIshikawa-Fujiwara, Tomokoja
dc.contributor.authorMatsui, Hideakija
dc.contributor.authorNaruse, Kiyoshija
dc.contributor.authorSakamoto, Naoakija
dc.contributor.authorUchiyama, Yasuoja
dc.contributor.authorTodo, Takeshija
dc.contributor.authorTakeda, Shunichija
dc.contributor.authorYamakado, Hodakaja
dc.contributor.authorTakahashi, Ryosukeja
dc.contributor.alternative上村, 紀仁ja
dc.contributor.alternative木下, 政人ja
dc.contributor.alternative内山, 安男ja
dc.contributor.alternative藤堂, 剛ja
dc.contributor.alternative武田, 俊一ja
dc.contributor.alternative山門, 穂高ja
dc.contributor.alternative髙橋, 良輔ja
dc.descriptionパーキンソン病の解明に役立つメダカの作製に成功 -メダカが神経変性疾患の研究に貢献できる可能性- 京都大学プレスリリース. 2015-04-09.ja
dc.description.abstractHomozygous mutations in the glucocerebrosidase (GBA) gene result in Gaucher disease (GD), the most common lysosomal storage disease. Recent genetic studies have revealed that GBA mutations confer a strong risk for sporadic Parkinson's disease (PD). To investigate how GBA mutations cause PD, we generated GBA nonsense mutant (GBA-/-) medaka that are completely deficient in glucocerebrosidase (GCase) activity. In contrast to the perinatal death in humans and mice lacking GCase activity, GBA-/- medaka survived for months, enabling analysis of the pathological progression. GBA-/- medaka displayed the pathological phenotypes resembling human neuronopathic GD including infiltration of Gaucher cell-like cells into the brains, progressive neuronal loss, and microgliosis. Detailed pathological findings represented lysosomal abnormalities in neurons and alpha-synuclein (α-syn) accumulation in axonal swellings containing autophagosomes. Unexpectedly, disruption of α-syn did not improve the life span, formation of axonal swellings, neuronal loss, or neuroinflammation in GBA-/- medaka. Taken together, the present study revealed GBA-/- medaka as a novel neuronopathic GD model, the pahological mechanisms of α-syn accumulation caused by GCase deficiency, and the minimal contribution of α-syn to the pathogenesis of neuronopathic GD.ja
dc.publisherPublic Library of Scienceja
dc.rightsc 2015 Uemura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ja
dc.titleViable Neuronopathic Gaucher Disease Model in Medaka (Oryzias latipes) Displays Axonal Accumulation of Alpha-Synuclein.ja
dc.type.niitypeJournal Articleja
dc.identifier.jtitlePLOS geneticsja
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