| Project/Area Number |
17K11316
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Ito Taku 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40401400)
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| Co-Investigator(Kenkyū-buntansha) |
川島 慶之 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (10376759)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | SLC26A4 / 前庭水管拡大 / 血管条 / 巨大耳石 / Mondini奇形 / 球形嚢 / 卵形嚢 / 半規管 / MicroCT / 遺伝子 / ゲノム / 脳・神経 |
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| Outline of Final Research Achievements |
The goal of this study is to elucidate the mechanism of inner ear impairment associated with SLC26A4 mutations and the development of Mondini malformation. In this study, it was considered that the degeneration of blood vessels in the stria vascularis and the proliferation of macrophages would cause the decrease of the endolymphatic potential in slc26a4 knockout mice. Gross morphological observation of otic capsules using microCT revealed that Mondini malformation might reflect on insufficient ossification of the cochlear modiolus. In addition, we have developed a novel mouse eye movement analysis device for the purpose of elucidating vestibular impairment in mice, which could lead to unveil the novel pathogenesis of dizziness and vertigo associated with SLC26A4 mutations in the future. These results may lead to the elucidation of the pathophysiology of inner ear disorders associated with SLC26A4 mutations and may lead to the development of new therapeutic agents.
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| Academic Significance and Societal Importance of the Research Achievements |
SLC26A4遺伝子変異に伴う患者さんでは、難聴の変動やふらつきが高頻度に観察される。難聴の変動は現在のところ薬剤で抑えることが困難であり、補聴器の調節や人工内耳の適応を考慮する点で時に判断を困難にする。また、ふらつきやめまいなどの平衡障害は生涯にわたって続く可能性があり、聴覚障害のようにデバイスによって対応することができない点で、患者さんのQOLを著しく落とす可能性がある。本研究成果はSLC26A4遺伝子変異に伴う患者さんで見られる難聴の変動やふらつきの病態解明に迫るものであり、新たな治療薬開発へとつながる可能性がある。
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