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Understanding flagellum formation in mouse spermatozoa

Research Project

Project/Area Number 18K14715
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionOsaka University

Principal Investigator

Castaneda Julio  大阪大学, 微生物病研究所, 特任助教(常勤) (00791659)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsspermatogenesis / sperm / N-DRC / sperm motility / male fertility / hydrocephalus / flagellum / cilia / fertility / sperm function / mice / CRISPR/Cas9 / spermatozoa
Outline of Final Research Achievements

My proposal set out the examine cilia and flagella formation by studying 3 components of the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is a macromolecular protein complex that helps regulate the beating motion of flagella and cilia as well as their formation. Flagella and cilia are important for cell and organ function. The N-DRC is composed of 11 subunits (DRC1-11). Eight N-DRC components have been studied in the mouse that lead to various phenotypes such as abnormal organ development (DRC1), short sperm tails (Drc7), immotile sperm (Drc5/Tcte1), or no phenotype at all (Drc6/Fbxl13). The remaining genes yet to be studied include DRC2, 10 (Iqcd), and 11 (Iqca). Using CRISPR/Cas9, I managed to knockout all 3 genes. I found that Drc2 knockout mice are perinatal lethal and exhibit hydrocephalus. Drc11/Iqca mice are fertile with no apparent abnormalities, while Drc10/Iqcd analysis is still ongoing.

Academic Significance and Societal Importance of the Research Achievements

The N-DRC is an important macromolecular complex that help regulate flagella and cilia formation and function. My research examined the last remaining components of the N-DRC that have yet to be studied. This research completes the analysis of all components of the N-DRC.

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] CRISPR/Cas9-based gene knockout in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction2020

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

      Biology of Reproduction

      Volume: 102 Pages: 1-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TESMIN, METALLOTHIONEIN-LIKE 5, is required for spermatogenesis in mice.2020

    • Author(s)
      Oji A, Isotani A, Fujihara Y, Castaneda JM, Oura S, Ikawa M.
    • Journal Title

      Biology of Reproduction

      Volume: 102 Issue: 4 Pages: 975-983

    • DOI

      10.1093/biolre/ioaa002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mouse t-complex protein 11 is important for progressive motility in sperm†2019

    • Author(s)
      Castaneda Julio M、Miyata Haruhiko、Archambeault Denise R、Satouh Yuhkoh、Yu Zhifeng、Ikawa Masahito、Matzuk Martin M
    • Journal Title

      Biology of Reproduction

      Volume: 102 Issue: 4 Pages: 852-862

    • DOI

      10.1093/biolre/ioz226

    • Related Report
      2019 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Spar1 is a novel transmembrane gene required for acrosome formation in mice2019

    • Author(s)
      Julio M Castaneda
    • Organizer
      Society for the Study of Reproduction
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spar1 is a novel transmembrane gene required for acrosome formation in mouse2018

    • Author(s)
      Julio Castaneda
    • Organizer
      Society for the Study of Reproduction
    • Related Report
      2018 Research-status Report
  • [Presentation] Spar1 is a novel transmembrane gene required for acrosome formation in mouse2018

    • Author(s)
      Julio Castaneda
    • Organizer
      Germ Cells Meeting, Cold Spring Harbor
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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