Pathological analysis and drug screening of hereditary progressive deafness DFNA5 using human iPS cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16856
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Keio University
• Principal Investigator: HOSOYA Makoto 慶應義塾大学, 医学部(信濃町), 助教 (30645445)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 遺伝性難聴

Outline of Final Research Achievements

A mutation of DFNA5 gene was introduced into normal human iPS cells using the CRISPR / Cas9 system to obtain DFNA5 mutant human iPS cells. DFNA5 is known as a deafness gene, and in order to elucidate the mechanism of deafness caused by this gene, we induced inner ear cells from this iPS cell and attempted a comparative study with normal iPS-derived inner ear cells. We investigated how abnormal DFNA5 causes disease in inner ear cells that express mutated DFNA5 protein, and clarified its molecular biological characteristics.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

遺伝性難聴の原因となる難聴遺伝子の一つであるDFNA5遺伝子に注目して研究を展開した。これまでいくつかの難聴遺伝子においてヒトiPS細胞を用いた研究が有用であることが示されているが、DFNA5遺伝子変異においてもヒトiPS細胞を用いた研究が有用であることが示された。今後、同様の手法によってさまざまな検討が進むことにより難聴遺伝子の分子生物学的な機序の解明と治療薬の開発などにつながる可能性があり、学術的意義や社会的意義が高い研究手法と考えられる。