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Discovery of genes essential for male fertility using CRISPR/Cas9-based genome editing technology

Research Project

Project/Area Number 18K16735
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionOsaka University

Principal Investigator

Lu Yonggang  大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00817033)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
KeywordsMale reproduction / Sperm-egg fusion / Fertilization / CRISPR/Cas9 / Knockout / Mouse model / Male contraception / Spermatology / male reproduction / male contraception / sperm / sperm-egg fusion / sperm function / sperm-oocyte fusion / Sperm / Spermatogenesis / Testis / Genome editing / Male fertility / Reproductive biology / Male infertility / Gene knockout
Outline of Final Research Achievements

During the four-year funding period, the applicant has generated multiple knockout mouse lines lacking testis-specific genes and analyzed the resultant phenotype. This study demonstrates the feasibility and efficiency of using the CRISPR/Cas9-mediated knockout strategy to identify genes essential for male reproduction. Through the large-scale in vivo screening, we have discovered essential genes Lrrc23, C2cd6, Sof1, Tmem95, and Fimp, which play roles in regulating sperm motility and sperm-egg fusion. The relevant research outcomes have been published in international peer-reviewed journals.

Academic Significance and Societal Importance of the Research Achievements

My work provides explanations for idiopathic male infertility. The identified molecules may serve as biomarkers for male infertility and potential targets for non-hormonal male contraception.

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2022 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 11 results,  Open Access: 11 results)

  • [Journal Article] Sperm membrane proteins DCST1 and DCST2 are required for sperm-egg interaction in mice and fish2022

    • Author(s)
      Noda Taichi、Blaha Andreas、Fujihara Yoshitaka、Gert Krista R.、Emori Chihiro、Deneke Victoria E.、Oura Seiya、Panser Karin、Lu Yonggang、Berent Sara、Kodani Mayo、Cabrera-Quio Luis Enrique、Pauli Andrea、Ikawa Masahito
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s42003-022-03289-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane2022

    • Author(s)
      Hwang Jae Yeon、Wang Huafeng、Lu Yonggang、Ikawa Masahito、Chung Jean-Ju
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 3 Pages: 110226-110226

    • DOI

      10.1016/j.celrep.2021.110226

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sperm IZUMO1 Is Required for Binding Preceding Fusion With Oolemma in Mice and Rats2022

    • Author(s)
      Matsumura Takafumi、Noda Taichi、Satouh Yuhkoh、Morohoshi Akane、Yuri Shunsuke、Ogawa Masaki、Lu Yonggang、Isotani Ayako、Ikawa Masahito
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 1-10

    • DOI

      10.3389/fcell.2021.810118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice2021

    • Author(s)
      Zhang Xin、Sun Jiang、Lu Yonggang、Zhang Jintao、Shimada Keisuke、Noda Taichi、Zhao Shuqin、Koyano Takayuki、Matsuyama Makoto、Zhou Shushu、Wu Jiayan、Ikawa Masahito、Liu Mingxi
    • Journal Title

      Journal of Cell Science

      Volume: 134 Issue: 20 Pages: 1-14

    • DOI

      10.1242/jcs.259381

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization2021

    • Author(s)
      Qu Yongcun、Chen Qi、Guo Shanshan、Ma Chiyuan、Lu Yonggang、Shi Junchao、Liu Shichao、Zhou Tong、Noda Taichi、Qian Jingjing、Zhang Liwen、Zhu Xili、Lei Xiaohua、Cao Yujing、Li Wei、Li Wei、Plachta Nicolas、Matzuk Martin M.、Ikawa Masahito、Duan Enkui、Zhang Ying、Wang Hongmei
    • Journal Title

      Protein & Cell

      Volume: 12 Issue: 10 Pages: 810-817

    • DOI

      10.1007/s13238-021-00825-y

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-based genome editing in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction2020

    • Author(s)
      Sun Jiang、Lu Yonggang、Nozawa Kaori、Xu Zoulan、Morohoshi Akane、Castaneda Julio M、Noda Taichi、Miyata Haruhiko、Abbasi Ferheen、Shawki Hossam H、Takahashi Satoru、Devlin Darius J、Yu Zhifeng、Matzuk Ryan M、Garcia Thomas X、Matzuk Martin M、Ikawa Masahito
    • Journal Title

      Biology of Reproduction

      Volume: N/A Issue: 2 Pages: 183-194

    • DOI

      10.1093/biolre/ioaa083

    • NAID

      120007190927

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice2020

    • Author(s)
      Taichi Noda, Yonggang Lu, Yoshitaka Fujihara, View ORCID ProfileSeiya Oura, View ORCID ProfileTakayuki Koyano, Sumire Kobayashi, Martin M. Matzuk, and View ORCID ProfileMasahito Ikawa
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 21 Pages: 11493-11502

    • DOI

      10.1073/pnas.1922650117

    • NAID

      120006957465

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice2020

    • Author(s)
      Fujihara Yoshitaka、Lu Yonggang、Noda Taichi、Oji Asami、Larasati Tamara、Kojima-Kita Kanako、Yu Zhifeng、Matzuk Ryan M.、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 17 Pages: 9393-9400

    • DOI

      10.1073/pnas.1917060117

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prss55 but not Prss51 is required for male fertility in mice†2020

    • Author(s)
      Kobayashi Kiyonori、Endo Tsutomu、Matsumura Takafumi、Lu Yonggang、Yu Zhifeng、Matzuk Martin M、Ikawa Masahito
    • Journal Title

      Biology of Reproduction

      Volume: - Issue: 2 Pages: 223-234

    • DOI

      10.1093/biolre/ioaa041

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CIB4 Is Essential for the Haploid Phase of Spermatogenesis in Mice2020

    • Author(s)
      Zoulan Xu, Haruhiko Miyata, Yuki Kaneda, Julio M Castaneda, Yonggang Lu, Akane Morohoshi, Zhifeng Yu, Martin M Matzuk, Masahito Ikawa
    • Journal Title

      Biology of Reproduction

      Volume: 102 Issue: 2 Pages: 1-9

    • DOI

      10.1093/biolre/ioaa059

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice†2019

    • Author(s)
      Yonggang Lu, Oura Seiya, Matsumura Takafumi, et al.
    • Journal Title

      Biology of Reproduction

      Volume: 101 Issue: 2 Pages: 501-511

    • DOI

      10.1093/biolre/ioz103

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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