| Project/Area Number |
18K16851
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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 56050:Otorhinolaryngology-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Ninoyu Yuzuru 京都府立医科大学, 医学(系)研究科(研究院), 助教 (70814573)
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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 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 感音難聴 / DFNA1 / 遺伝性難聴 / 新規DFNA1変異 / 頂側面結合 / 聴毛 / リボンシナプス / DIAPH1 |
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| Outline of Final Research Achievements |
We established two types of DFNA1 mouse model(DIA1-TG,DIA1-KI) expressing novel DFNA1 mutant (R1204X/R1213X), which revealed the expression cell types and subcellular localization of DIA1 in the cochlea. The mutant was localized at the apical junctional complexes(AJC) of cochlear hair cells, where showed morphological abnormalities. Moreover, noise exposure induced significant decrement of the ribbon synapses and stereocilia abnormalities in cochlear hair cells in the mutant mice, suggesting subclinical vulnerability of cochlear hair cells. In conclusion, AJC is the main lesion of DFNA1 and subclinical vulnerability of cochlear hair cells is likely the cause of progressive hearing loss associated with DFNA1.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性難聴の6割は遺伝性難聴を言われ、その発生頻度は1000人に1人と高頻度にも関わらず、未だ根本的な治療法は開発されていない。本研究では遺伝性難聴の一つDFNA1の進行性難聴発症機序を、アクチン骨格制御機構の観点から解明し、蝸牛におけるその難聴責任部位を明らかにした。これは将来的なDFNA1の治療薬開発のみならず、加齢性難聴をはじめとした進行性感音難聴治療薬開発につながることが期待できる。
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