Identification of novel genes responsible for sex differences of age-related hearing loss

Research Project

Project/Area Number	18K09364
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56050:Otorhinolaryngology-related
Research Institution	Tokyo Metropolitan Institute of Medical Science
Principal Investigator	YASUDA Shumpei 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主任研究員 (50534012)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords	加齢性難聴 / マウス / シングルセルRNA-seq / 外有毛細胞 / 順遺伝学 / scRNA-seq / ゲノムマッピング / ABR / 遺伝学 / 難聴 / DPOAE
Outline of Final Research Achievements	BALB/cA mice, a sub-strain of BALB/c mice, develop early-onset high frequency-specific age-related hearing loss (ARHL), while BALB/cByJ mice, another sub-strain of BALB/c mice, are resistant to the ARHL. Preliminary studies indicate that the susceptibility of BALB/cA to the onset of ARHL is caused by multiple responsible genes, at least one of which is located on the X chromosome. Since the genes responsible for the onset of ARHL on the X chromosome have not been reported, we performed X chromosome mapping using F2 individuals and single-cell RNA-seq to compare gene expression in outer hair cells to search for responsible genes. The genes with different expression among the sub-strains were selected as candidate genes.
Academic Significance and Societal Importance of the Research Achievements	ヒトの加齢性難聴は、その発症要因の1つとして遺伝的要因が報告されているが、その責任遺伝子はほとんど報告されておらず、発症の性差についても同様である。研究代表者は、ヒトで特定の難しい発症責任遺伝子の同定を目的に、研究用マウスを使用した責任遺伝子の探索を進めている。本研究では、加齢性難聴の発症責任遺伝子であり、発症に性差をもたらす可能性のある遺伝子の候補を初めてピックアップすることができた。これは、発症の性差を考える上で、また、責任遺伝子を同定し、加齢性難聴の発症予防および治療に活かすための重要なステップであると考えられる。