2021 Fiscal Year Final Research Report

Establishment and applications of model mice with fluctuated deafness by advanced gene-engineering methods

Research Project

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Project/Area Number	18H04062
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	Osaka University (2020-2021) Niigata University (2018-2019)
Principal Investigator	Hibino Hiroshi 大阪大学, 医学系研究科, 教授 (70314317)
Co-Investigator(Kenkyū-buntansha)	澤村晴志朗大阪大学, 医学系研究科, 助教 (10781974) 増田正次杏林大学, 医学部, 准教授 (20317225) 田中謙二慶應義塾大学, 医学部(信濃町), 教授 (30329700) 神崎晶慶應義塾大学, 医学部(信濃町), 講師 (50286556) 崔森悦新潟大学, 自然科学系, 准教授 (60568418) 任書晃岐阜大学, 大学院医学系研究科, 教授 (80644905) 永森收志東京慈恵会医科大学, 医学部, 准教授 (90467572)
Project Period (FY)	2018-04-01 – 2022-03-31
Keywords	内耳 / 難聴 / 光遺伝学 / 薬剤誘導性遺伝子制御
Outline of Final Research Achievements	Hearing loss induced by disorder of the cochlea of the inner ear affects ~10% of the global population and thus it provides a great clinical impact. The onset and progress are characterized by different time course―sudden or slow type. Fluctuating type often becomes severe and irreversible deafness. To overcome this deafness type, in the present study we described two deaf animal models by genetic modifications targeting stria vascularis, an epithelial tissue that maintains unique ionic and electrical properties of the cochlea. The mouse line showed slowly progressing hearing loss in response to drug-induced knockdown of an ion transporter in the stria. The other line expressed a light-gated ion channel in the stria and exhibited sudden deafness by optogenetic stimulation. In both mouse types, hearing was recovered after cessation of the perturbation. We also revealed a mechanism underlying hearing loss in each model. This work may contribute to translational research for deafness.
Free Research Field	薬理学
Academic Significance and Societal Importance of the Research Achievements	本研究では、ヒトで見られる変動性難聴の症状を模倣する「緩徐進行型」難聴および「急性発症型」難聴の動物モデルを樹立した。これらのモデルは、内耳蝸牛の電気的環境を司る上皮様組織「血管条」の機能を、それぞれ薬物投与および光照射によって制御することで、聴力の悪化と回復を反復させることができる、これまでにない難聴モデルである。本研究の成果は、症状の反復によって難聴が重症化および難治化する機序の解明や、変動性難聴の治療・予防法開発に貢献することが期待される。