論文 - 詳細
| RRC ID | 33327 |
|---|---|
| 著者 | Uemura N, Koike M, Ansai S, Kinoshita M, Ishikawa-Fujiwara T, Matsui H, Naruse K, Sakamoto N, Uchiyama Y, Todo T, Takeda S, Yamakado H, Takahashi R. |
| タイトル | Viable neuronopathic Gaucher disease model in Medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein. |
| ジャーナル | PLoS Genet |
| 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. |
| 巻・号 | 11(4) |
| ページ | e1005065 |
| 公開日 | 2015-4-1 |
| DOI | 10.1371/journal.pgen.1005065 |
| PII | PGENETICS-D-14-03033 |
| PMID | 25835295 |
| PMC | PMC4383526 |
| MeSH | Animals Axons / metabolism* Axons / ultrastructure Disease Models, Animal Gaucher Disease / genetics* Gaucher Disease / metabolism Gaucher Disease / pathology Glucosylceramidase / deficiency* Glucosylceramidase / genetics Oryzias / genetics* Oryzias / metabolism Phagosomes / metabolism alpha-Synuclein / metabolism* |
| IF | 5.175 |
| 引用数 | 32 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| メダカ | TILLING_MUTANT Kyoto-Cab (OK-Cab(MT830)) |