• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the mechanism of hearing loss associated with distal tubular acidosis

Research Project

Project/Area Number 21K07756
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionOita University

Principal Investigator

Ikeuchi Mayo  大分大学, 医学部, 医員 (80865668)

Co-Investigator(Kenkyū-buntansha) 井上 真紀  大分大学, 医学部, 講師 (20726913)
清田 今日子  大分大学, 医学部, 医員 (30774492)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords遠位尿細管性アシドーシス / 難聴 / ゼブラフィッシュ / リソソーム / pH
Outline of Research at the Start

遺伝性の遠位尿細管性アシドーシス(distal renal tubular acidosis : dRTA)は、腎の集合管におけるV-ATPaseの異常により、代謝性アシドーシスを来す疾患であり、感音性難聴の合併も多いが、感音性難聴の発症時期や機序は解明されていない。dRTAの原因遺伝子であるATP6V1B1は内耳の内リンパ嚢にも発現してpH調整をしており、内耳での酸分泌障害が感音性難聴の発症に関与している可能性が高い。本研究はゼブラフィッシュを用いて、ATP6V1B1遺伝子変異による内耳での酸塩基平衡における障害と難聴の関連を検討し、dRTAにおける感音性難聴発症のメカニズム解明を目指す。

Outline of Final Research Achievements

We analyzed the pathogenesis of sensorineural hearing loss associated with dRTA caused by the atp6v1b1 variant, one of the genes responsible for hereditary distal tubular acidosis. Ortholog gene, atp6v1ba-deficient zebrafish inner ear hair cells showed brittle cilia and autophagosome formation. LC3B, a marker of autophagosome formation, was strongly stained in hair cells. Lysosomal staining using the fluorescent dyes indicated a link between autophagy failure and hair cell degeneration due to pH imbalance inside lysosomes. Our research provided new insights into the understanding of this pathology and its treatment.

Academic Significance and Societal Importance of the Research Achievements

ゼブラフィッシュモデルは、その透明性により内耳が直接可視化可能であり、創薬のin vivoスクリーニングにも十分な実績を持つことから、本疾患モデルは将来の新たな治療法開発にも貢献する可能性がある。
本研究において作製したatp6v1ba欠損ゼブラフィッシュモデルやpHluorin2トランスジェニックモデルは、アシドーシスに関連した聴覚障害の疾患メカニズムや潜在的治療法をさらに研究するための貴重なツールとなりうる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2024 2023

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Funded Workshop (1 results)

  • [Journal Article] A pH imbalance is linked to autophagic dysregulation of inner ear hair cells in Atp6v1ba-deficient zebrafish2024

    • Author(s)
      Ikeuchi Mayo、Inoue Masanori、Miyahara Hiroaki、Sebastian Wulan Apridita、Miyazaki Shuya、Takeno Takashi、Kiyota Kyoko、Yano Shinji、Shiraishi Hiroshi、Shimizu Nobuyuki、Hanada Reiko、Yoshimura Akihiko、Ihara Kenji、Hanada Toshikatsu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 699 Pages: 149551-149551

    • DOI

      10.1016/j.bbrc.2024.149551

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ゼブラフィッシュを用いた遠位尿細管性アシドーシスの難聴発症メカニズム解明2023

    • Author(s)
      池内 真代
    • Organizer
      日本生化学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Elucidation of the mechanism of hearing loss associated with distal tubular acidosis2023

    • Author(s)
      池内 真代
    • Organizer
      Asian Conference on Fish Models for Diseases2023
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遠位尿細管性アシドーシスに伴う難聴発症のメカニズム解明2023

    • Author(s)
      池内 真代
    • Organizer
      日本生化学会九州支部例会
    • Related Report
      2023 Annual Research Report
  • [Funded Workshop] Asian Conference on Fish Models for Diseases20232023

    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi