| Project/Area Number |
17K16292
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Institute for Developmental Research Aichi Developmental Disability Center |
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Principal Investigator |
Ueda Masashi 愛知県医療療育総合センター発達障害研究所, 細胞病態研究部, リサーチレジデント (90791541)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | ZTTK症候群 / SONハプロ不全 / 知的障害 / 神経細胞移動 / 樹状突起スパイン形成 / シナプス形成 / 神経細胞移動の阻害 / 樹状突起スパイン形成の阻害 / 発生・分化 |
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| Outline of Final Research Achievements |
This study has been carried out to clarify a role of SON, a causing gene of ZTTK syndrome, in the brain formation during development. To examine the effects of SON-knockdown on mammalian brain development, we electroporated the shRNA constructs into the lateral ventricles of mouse brain at embryonic day 14 (E14). Neural progenitor cells in a SON-KD state did not effectively migrate to upper cortical plate at E18. Interestingly, at postnatal day 60, the numbers of the dendritic spines ofneurons in a SON-KD state were reduced compared with those in normal state. These impairments were rescued by overexpression of human full-length SON, but not with a disease-related truncation mutant, lacking most functional domains.
These data suggest that sufficient SON protein is critical to cortical neuronal migration and dendritic spine formations during development in mouse brain.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により胎生期のSON蛋白質の量的低下が、神経細胞移動やシナプス形成の障害を引き起こす事で知的障害をもたらす可能性が強く示された。またヒトSON蛋白質を補充することによりこれらの細胞障害が改善されるという結果は、ZTTK症候群の治療戦略として薬剤や遺伝子治療によるSON蛋白質量の是正が有効であることを示唆している。
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