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Title: Viable Neuronopathic Gaucher Disease Model in Medaka (Oryzias latipes) Displays Axonal Accumulation of Alpha-Synuclein.
Authors: Uemura, Norihito  kyouindb  KAKEN_id  orcid (unconfirmed)
Koike, Masato
Ansai, Satoshi
Kinoshita, Masato
Ishikawa-Fujiwara, Tomoko
Matsui, Hideaki
Naruse, Kiyoshi
Sakamoto, Naoaki
Uchiyama, Yasuo
Todo, Takeshi
Takeda, Shunichi
Yamakado, Hodaka  kyouindb  KAKEN_id
Takahashi, Ryosuke  kyouindb  KAKEN_id
Author's alias: 上村, 紀仁
木下, 政人
内山, 安男
藤堂, 剛
武田, 俊一
山門, 穂高
髙橋, 良輔
Issue Date: 2-Apr-2015
Publisher: Public Library of Science
Journal title: PLOS genetics
Volume: 11
Issue: 4
Thesis number: e1005065
Abstract: Homozygous 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.
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.
Rights: c 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.
DOI(Published Version): 10.1371/journal.pgen.1005065
PubMed ID: 25835295
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