| Project/Area Number |
17K16268
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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 | National Hospital Organization, Kyushu Medical Center (Clinical Institute) |
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Principal Investigator |
Matsushita Yuki 独立行政法人国立病院機構九州医療センター(臨床研究センター), その他部局等, 小児科医師 (50778868)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | shank3a / 自閉スペクトラム症 / 感覚過敏 / 脳内分子シグナル / 興奮抑制バランス / ニューロン分化成熟 / 興奮性シナプス / 神経科学 / 環境 / 動物 |
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| Outline of Final Research Achievements |
SHANK3(SH3 and ankyrin repeat domain containing 3)is one of the causative genes of 22q13 deletion syndrome and autism spectrum disorder. Among SHANK3 products, the SHANK3a isoform is the biggest in molecular weight, with ankyrin repeats domain (ARD) at the N-terminal. I performed a comprehensive search using immunoprecipitation - mass spectrometry to clarify functional significance of ARD. As a result, I found that ARD had a possibility to control the molecular signal which was important to the neural differentiation and maturation. In addition, SHANK3a might control neural excitation/inhibition balance early after birth. I concluded that it was essential isoform in building a functional circuit.
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| Academic Significance and Societal Importance of the Research Achievements |
自閉スペクトラム症(ASD)罹患児は聴覚・味覚・触覚上の過敏徴候を示すことが多く、その感覚過敏は養育上大きな障壁となる。最近、Orefice らは末梢神経におけるSHANK3欠損モデルを作成し、感覚過敏に関わる分子メカニズムの一端を明らかにした(Orefice LL, Cell 2019)。しかし、このような臨床的特徴を来たす脳内メカニズムはこれまで明らかにされていない。今回の研究成果は、ASD児における感覚過敏のメカニズムを説明する上で、重要な手がかりを与えた。
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