| Project/Area Number |
18K15662
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Niigata University |
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Principal Investigator |
Nyuzuki Hiromi 新潟大学, 医歯学総合病院, 医員 (80793926)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | PNPLA4 / ミトコンドリア呼吸鎖異常症 / 乳児突然死 / ゼブラフィッシュ / ミトコンドリア異常症 / 脂質代謝異常 / 脂質代謝 |
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| Outline of Final Research Achievements |
The purpose of this study was to clarify the molecular biological functions of PNPLA4, the gene responsible for mitochondrial respiratory chain disorders associated with sudden infant death. First, we generated PNPLA4 knockout zebrafish using the CRISPR/Cas9 system. Then, we confirmed the distribution of PNPLA4 mRNA expression by in situ hybridization and other methods. Furthermore, we performed comprehensive lipid analysis, protein expression analysis, and RNA-seq analysis of knockout zebrafish brain samples, and found significant changes in metabolites and gene expression related to lipid and energy metabolism. Through these studies, we have elucidated one aspect of the function of PNPLA4.
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| Academic Significance and Societal Importance of the Research Achievements |
小児の進行性希少難病であるミトコンドリア呼吸鎖異常症の病態は未だ不明な点が多く、個々の原因遺伝子の詳細な機能を明らかにすることが病態解明の鍵となる。本研究を通じて、乳児突然死として発症したミトコンドリア呼吸鎖異常症の原因遺伝子の一つであるPNPLA4の機能の一側面が明らかとなった。今後のミトコンドリア呼吸鎖異常症の病態解明につながる大きな成果であり、将来的に新たな治療戦略の創出並びに乳児突然死の予防法提唱に寄与する可能性がある。
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