Comprehensive screening of genetic factors by using mouse models of age-related hearing loss in human for clinical application

2014 Fiscal Year Final Research Report

• Project/Area Number: 23300160
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KIKKAWA Yoshiaki 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, プロジェクトリーダー (20280787)
• Co-Investigator(Kenkyū-buntansha): SHITARA Hiroshi 公益財団法人東京都医学総合研究所, 基盤技術研究センター, 主任基盤技術研究職員 (90321885) ; NOGUCHI Yoshihiro 東京医科歯科大学, 医学部附属病院, 講師 (50282752) ; WADA Kenta 東京農業大学, 生物産業学部, 助教 (20508113)
• Research Collaborator: SUZUKI Sari 東京農業大学, 大学院生物産業学研究科 ; MIYASAKA Yuki 新潟大学, 大学院医歯学総合研究科 ; OBARA Yo 筑波大学, 大学院生命環境科学研究科
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 遺伝学 / 遺伝子 / ゲノム / 加齢性難聴 / 難聴モデルマウス / QTL / コンソミック系統 / Lrrc30

Outline of Final Research Achievements

We performed quantitative trait locus (QTL) linkage analysis and comprehensive gene expression analysis to identify the susceptibility and resistance genes in the onset of age-related hearing loss (AHL) by using mouse models of human AHL. QTL linkage analysis showed that the multiple susceptibility loci on chromosome 5 were involved in early-onset AHL of the DBA/2J mice. QTL linkage analysis also suggested that the hearing loss in NOD/Shi mice developed owing to the effects of the susceptibility loci on chromosomes 1, 5, 6, 9, and 10. Moreover, AHL in the C57BL/6J mice was suppressed by transgenesis of AHL resistance MSM/Ms mice-derived genomic DNA, including the leucine-rich repeat containing 30 gene (Lrrc30) on chromosome 17; the suppression of AHL in C57BL/6J mice was caused by the increased Lrrc30 expression following the transgenesis. These findings on AHL-related loci and genes in mice might be useful in the genetic diagnosis of AHL in humans.

Free Research Field

実験動物学