| Project/Area Number |
17H04042
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
Ueyama Takehiko 神戸大学, バイオシグナル総合研究センター, 准教授 (80346254)
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| Co-Investigator(Kenkyū-buntansha) |
坂口 博史 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00515223)
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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 |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 感音難聴 / DFNA1 / DIAPH1 / DIA1 / 遺伝性難聴 / 進行性難聴 / 血液異常 / 遺伝 / ＤＩＡ１ |
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| Outline of Final Research Achievements |
1. Noise exposure induced significantly decreased number of the ribbon synapse in hair cells in mice expressing a DIA1 mutant (p.R1213X) compared with control mice, suggesting that noise is one of factors leading to progressive hearing loss in DFNA1 patients.
2. In mice expressing the DIA1 mutant, the mutant was localized at the apical junctional complex (AJC) of hair cells, where showed morphological abnormalities by TEM. Thus, AJC is likely the main lesion in DFNA1.
3. In aged mice expressing the DIA1 mutant, size of the platelets was spread over a wider range, compared with control mice. Detailed studies analyzing the mechanism manifesting the phenotype are going on.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝性感音難聴の一病型であるDFNA1の進行性難聴の発症機序を解明した。1. 主要病変部位は、変異体が局在する蝸牛有毛細胞の頂側結合である、2. 騒音により有毛細胞内のリボンシナプス数が減少する。
これらは、DFNA1の治療戦略上、大きな成果である。現在、引き続きDFNA1の治療薬開発を進めているが、本研究の継続・成功により、有効な治療薬のない感音難聴の治療法開発の扉を開けることが出来ると確信している。
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