| Project/Area Number |
18K16904
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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 | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 遺伝子難聴 / 幹細胞ホーミング機構 / 蝸牛ギャップ結合 / 遺伝性難聴 / ギャップ結合 / 蝸牛 |
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| Outline of Final Research Achievements |
Brn4 is a transcription factor involved in the differentiation of neurons and cochlear cells and is known to be the causative gene of X-linked deafness type 3 (DFN3), the most common form of X-linked nonsyndromic deafness, although the mechanism of this disease remains largely unknown. The principal investigator has discovered that Brn4-deficient mice and CX26(GJB2) mutant mice, the most common type of congenital deafness, share a common molecular pathogenesis called "gap junction complex disruption". This discovery is expected to lead to the development of therapies targeting gap junction complexes for this disease as well. In this study, we identified that the initial cellular degeneration is in cochlear fibrocyte that form gap junction complexes, determined the optimal conditions for bone marrow mesenchymal stem cell transplantation into the inner ear of mice using cochlear fibrocyte and their gap junctions, and developed a inner ear cell therapy for hearing loss.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性高度難聴の約半数は遺伝子の関与があるといわれている。原因となる遺伝子産物の1つであるBrn4はニューロンや、蝸牛細胞の分化に関わる転写因子でありX染色体性の非症候性難聴では最多の疾患であるX-linked deafness type3（DFN3）の原因遺伝子として知られているが、その機序は未だ不明であり、その解明が求められている、本研究ではその解明および幹細胞ホーミング機構と呼ばれる分子機構の活性化の解析を行うことで内耳の標的組織への侵入能力の高い細胞、内耳誘導性の間葉系幹細胞の探索を行っており、将来的に新たな治療技術の可能性が示すことができ、学術的および社会的意義は極めて高い。
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