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Elucidation of the pathogenesis of azoospermia caused by deficiency of the RNA-binding protein RBM10 and exploration of treatment methods

Research Project

Project/Area Number 19K08327
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 InstitutionOsaka Metropolitan University (2022-2023)
Osaka City University (2019-2021)

Principal Investigator

Kunimoto Hiroyuki  大阪公立大学, 大学院医学研究科, 助教 (80372853)

Co-Investigator(Kenkyū-buntansha) 濱崎 考史  大阪公立大学, 大学院医学研究科, 教授 (40619798)
井上 晃  大阪公立大学, 大学院医学研究科, 研究員 (50109857)
中嶋 弘一  大阪公立大学, 大学院医学研究科, 特別研究員 (00227787)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords精子形成不全 / 男性不妊症 / 選択的スプライシング / 精子形成
Outline of Research at the Start

RNA-binding motif protein 10(RBM10:別名S1-1)は、選択的スプライシングに関与するRNA結合タンパクである。我々は予備実験から、RBM10欠損が不妊症の原因となる可能性を示唆する結果を得た。
本研究では、マウスを用いて、RBM10を臓器あるいは時間特異的に欠損させることでRBM10欠損が不妊症の原因となり得るかの検証およびその発症機序の解明を目的とする。

Outline of Final Research Achievements

RBM10 is an RNA-binding protein involved in alternative splicing. We examined whether RBM10 is involved in spermatogenesis using RBM10-deficient mice. We found that RBM10-deficient mice show testicular atrophy and are deficient in spermatogenesis. We also found a group of mRNAs whose expression was altered in RBM10-deficient testes.

Academic Significance and Societal Importance of the Research Achievements

近年、挙児希望にもかかわらず不妊症と診断されるカップルが増加傾向にあり、少子化問題が日本の最も深刻な社会問題の一つとなっています。不妊症の原因の約50%は男性側にあるとされ、その主たる原因である精子形成不全は原因不明のため発症機序の解明が待たれています。我々はRBM10が精子形成をどの様に制御するのかを明らかにすることで、男性不妊症患者に福音となるような治療法の開発を目指しています。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (8 results)

All 2023 2021 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (3 results)

  • [Journal Article] Sequestration of RBM10 in Nuclear Bodies: Targeting Sequences and Biological Significance2021

    • Author(s)
      Wang Ling-Yu、Xiao Sheng-Jun、Kunimoto Hiroyuki、Tokunaga Kazuaki、Kojima Hirotada、Kimura Masatsugu、Yamamoto Takahiro、Yamamoto Naoki、Zhao Hong、Nishio Koji、Tani Tokio、Nakajima Koichi、Sunami Kishiko、Inoue Akira
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10526-10526

    • DOI

      10.3390/ijms221910526

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RBM10: Structure, functions, and associated diseases2021

    • Author(s)
      Inoue Akira
    • Journal Title

      Gene

      Volume: 783 Pages: 145463-145463

    • DOI

      10.1016/j.gene.2021.145463

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4‐STIL complexes in the nucleus2020

    • Author(s)
      Kunimoto Hiroyuki、Inoue Akira、Kojima Hirotada、Yang Junhao、Zhao Hong、Tsuruta Daisuke、Nakajima Koichi
    • Journal Title

      Genes to Cells

      Volume: 25(2) Issue: 2 Pages: 100-110

    • DOI

      10.1111/gtc.12741

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phospho-Ser727 triggers a multistep inactivation of STAT3 by rapid dissociation of pY705?SH2 through C-terminal tail modulation2020

    • Author(s)
      Yang Junhao、Kunimoto Hiroyuki、Katayama Bumpei、Zhao Hong、Shiromizu Takashi、Wang Lingyu、Ozawa Toshiyuki、Tomonaga Takeshi、Tsuruta Daisuke、Nakajima Koichi
    • Journal Title

      International Immunology

      Volume: 32(2) Issue: 2 Pages: 73-88

    • DOI

      10.1093/intimm/dxz061

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Molecular Basis of Chemical Chaperone Therapy for Oculocutaneous Albinism Type 1A2018

    • Author(s)
      Ayako Teramae, Yui Kobayashi, Hiroyuki Kunimoto, Koichi Nakajima, Tamio Suzuki, Daisuke Tsuruta and Kazuyoshi Fukai
    • Journal Title

      J Invest Dermatol

      Volume: 139 Issue: 5 Pages: 1143-1149

    • DOI

      10.1016/j.jid.2018.10.033

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞核RNAスプライシング制御因子RBM10の中枢神経系及び末梢組織における発現と機能2023

    • Author(s)
      山本 直樹、中谷 善彦、樫村 剛、熊谷 望海、須藤 千晴、塙 雄大、生井 莉奈子、黒川 信、國本 浩之、井上 晃
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] RBM10はHepG2において中心小体複製に関わる新規の調節因子である2019

    • Author(s)
      國本 浩之, 井上 晃, 趙 虹, 中嶋 弘一
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Tetramer-based model of STAT3 activation-inactivation2019

    • Author(s)
      Lingyu Wang, Hong Zhao, Junhao Yang, Hiroyuki Kunimoto, Koichi Nakajima
    • Organizer
      第48回 日本免疫学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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