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Generation of sex chromosome linked histone demethylase activity-converted mice and their effect on sex differentiation

Research Project

Project/Area Number 19K22369
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionKyushu University

Principal Investigator

Iwamori Naoki  九州大学, 農学研究院, 准教授 (70647362)

Co-Investigator(Kenkyū-buntansha) 岩森 督子  九州大学, 医学研究院, 助教 (10711509)
Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywords性決定 / 性染色体 / ヒストン脱メチル化酵素 / ゲノム編集 / UTX / UTY / 性差 / 性分化 / 性転換
Outline of Research at the Start

哺乳類の雌雄の間ではY染色体上遺伝子の発現の他に、性染色体上ヒストン脱メチル化酵素UTX及びUTYの活性が異なる。本研究ではUTX及びUTYにアミノ酸置換を導入し、UTXの脱メチル化活性をUTY型にまで減弱させた雌マウス、及びUTYの脱メチル化活性をUTX型にまで増強させた雄マウスを作製し、生殖腺、生殖細胞や脳の性分化への影響を調べ、UTX及びUTYの異なるH3K27脱メチル化活性が性分化制御に関与するかどうか明らかにする。

Outline of Final Research Achievements

UTX and UTY are H3K27 demethylases encoded on sex chromosomes. Since there is a large difference in their demethylase activity between UTX and UTY, the aim of this study is that whether the difference in demethylase activity is involved in sex determination or not is determined by conversion of H3K27 demethylase activity of male to the female level and vice versa. By referring to the amino acid sequences and crystal structures of UTX and UTY, multiple amino acid mutants which could convert UTX activity to UTY level (UTX ↓) and UTY activity to UTX level (UTY ↑) were prepared. best amino acid mutants were identified by evaluation using cultured cells. Then, although mice with the identified amino acid mutations were prepared by genome editing, no sex conversion was observed in both females with UTX ↓ and males with UTY ↑.

Academic Significance and Societal Importance of the Research Achievements

性は性染色体の遺伝的性で決定され、生殖線のみならず脳など様々な組織で性差が現れる。近年、LGBTなどの性の多様性が広く認識されるようになり、性差の制御にも多様性、連続性があるという考えが広まりつつある。本研究で対象とするUTXとUTYは活性が異なることから性差を構築する候補として考えられる。本研究結果によりUTX/UTYが雌雄の性決定に関わりがない可能性が高くなったことから、実際にUTX/UTY変異マウスが組織レベル、細胞レベルでの性差構築を解析する有用なツールとなることが示された。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Univ of Illinois at Urbana-Champaign/Carnegie Mellon University/Van Andel Research Institute(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Univ of Illinois at Urbana- Champaign/Carnegie Mellon University/Van Andel Research Institute(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Washington University School of Medicine(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Korea Brain Research Institute(韓国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Identification of TMCO2 as an acrosome‐associated protein during rat spermiogenesis2020

    • Author(s)
      Kaneko Takane、Toh Saori、Mochida Izumi、Iwamori Naoki、Inai Tetsuichiro、Iida Hiroshi
    • Journal Title

      Molecular Reproduction and Development

      Volume: 87 Issue: 7 Pages: 808-818

    • DOI

      10.1002/mrd.23396

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel localizations and interactions of intercellular bridge proteins revealed by proteomic profiling†2020

    • Author(s)
      Iwamori Tokuko、Iwamori Naoki、Matsumoto Masaki、Imai Hiroyuki、Ono Etsuro
    • Journal Title

      Biology of Reproduction

      Volume: 0 Issue: 5 Pages: 1134-1144

    • DOI

      10.1093/biolre/ioaa017

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase2020

    • Author(s)
      Byun Sangwon、Seok Sunmi、Kim Young-Chae、Zhang Yang、Yau Peter、Iwamori Naoki、Xu H. Eric、Ma Jian、Kemper Byron、Kemper Jongsook Kim
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 807-807

    • DOI

      10.1038/s41467-020-14384-z

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis2019

    • Author(s)
      Mallaney Cates、Ostrander Elizabeth L.、Celik Hamza、Kramer Ashley C.、Martens Andrew、Kothari Alok、Koh Won Kyun、Haussler Emily、Iwamori Naoki、Gontarz Paul、Zhang Bo、Challen Grant A.
    • Journal Title

      Leukemia

      Volume: 印刷中 Issue: 10 Pages: 2506-2521

    • DOI

      10.1038/s41375-019-0462-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Visualization of intercellular bridges and undifferentiated spermatogonia in in vitro differentiation of male germ cells2020

    • Author(s)
      Yuki Yamamura, Hiroshi Iida, Naoki Iwamori
    • Organizer
      第18回幹細胞シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] The role of H3K27 demethylases in the aging of spermatogonial stem cells2019

    • Author(s)
      Naoki Iwamori, Sakurako Shima, Tokuko Iwamori, Hiroshi Iida
    • Organizer
      ISSCR 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of Spermatogonial stem cells by H3K27 demethylases2019

    • Author(s)
      Sakurako Shima, Tokuko Iwamori, Hiroshi Iida, Naoki Iwamori
    • Organizer
      2019 SSR annual meeting (52nd)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ノックアウトマウスを用いたIntercellular bridge関連遺伝子KIAA1210の機能解析2019

    • Author(s)
      岩森督子、加藤譲、岩森巨樹、今井啓之、相賀裕美子、小野悦郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2022-01-27  

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