2022 Fiscal Year Final Research Report
Mechanistic analyses how arginine methylation drives cerebellar development
| Project/Area Number |
20K15913
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | アルギニンメチル化 / 小脳 / 小脳発達 / 顆粒細胞 |
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| Outline of Final Research Achievements |
PRMT1, a major arginine methyltransferase, plays critical roles in regulation of gene expression or cell proliferation. Although increasing number of studies demonstrate essential roles of PRMT1 in the brain development, its specific role in the cerebellum has not been studied yet.
Here, we have made a new genetically modified mice which lack Prmt1 gene specifically in the cerebellar granule cells, which is one of the major neuronal types in the cerebellum. Histological analysis of the cerebellar tissues revealed that PRMT1-knockout animals had severe defects in granule cell development at postnatal stages, peak of the cerebellar. Loss of PRMT1 affected proliferation of precursor of granule neurons, suggesting that PRMT1 positively regulates their proliferation. Furthermore, we have found that PRMT1 deficient mice has motor defects.
Our results demonstrate that PRMT1 is essential for the cerebellar development by regulation of granule cell development.
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| Free Research Field |
動物生化学
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| Academic Significance and Societal Importance of the Research Achievements |
小脳は運動機能、情動、認知機能など脳の主要機能の一部を司り、近年では小脳の発達障害と自閉症との関連も着目されている。
本研究は、タンパク質アルギニンメチル化を担う酵素：PRMT1が小脳顆粒細胞に強く発現することからその発達における機能に着目した。小脳機能を担う顆粒細胞で特異的にPRMT1を欠損したマウスを作製し解析した結果、小脳が小さく特に顆粒細胞の成熟が著しく低下することや運動機能異常を呈することが判明した。本研究結果はPRMT1が正常な小脳発達に必須の遺伝子であることを示しており、今後はPRMT1の小脳における標的分子の探索とともに、その小脳疾患との関係性の解明が必要である。
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