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Analysis of sperm function using ES chimeric mice

Research Project

Project/Area Number 17H04987
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionOsaka University

Principal Investigator

Miyata Haruhiko  大阪大学, 微生物病研究所, 准教授 (50604732)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords精子 / 鞭毛 / ゲノム編集 / キメラマウス / 不妊 / ダイニン / CRISPR/Cas9 / ES細胞 / 受精
Outline of Final Research Achievements

One of the causes of male infertility is impaired sperm motility and several causative genes have been reported. These genes are involved in not only sperm flagellar motility but also ciliary motility in the trachea and ventricles (PCD: primary ciliary dyskinesia), which results in postnatal lethality in knockout mice. In this study, (1) we established the ES cells which exhibit red fluorescence in the mitochondria and (2) chimeric mice were generated using the ES cells to avoid postnatal lethality, and the function of Hydin, which is the causative gene of PCD, was analyzed.

Academic Significance and Societal Importance of the Research Achievements

本研究では、HYDINがマウスの精子鞭毛形成に必須であることが明らかになった。HYDINは原発性繊毛運動不全症の原因遺伝子であり、繊毛の運動不全だけではなく精子鞭毛形成異常を示す可能性が示唆された。さらにDNAH8がマウスの精子鞭毛形成に必須であることも明らかになった。男性不妊患者でもDNAH8の変異を見つけており、DNAH8のさらなる機能解明は男性不妊の原因究明や治療法の開発に繋がると期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (36 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (17 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 17 results,  Open Access: 17 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] 復旦大学(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility2021

    • Author(s)
      Shimada Keisuke、Park Soojin、Miyata Haruhiko、Yu Zhifeng、Morohoshi Akane、Oura Seiya、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 6 Pages: 1-12

    • DOI

      10.1073/pnas.2018355118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/CAS9-mediated amino acid substitution reveals phosphorylation residues of RSPH6A are not essential for male fertility in mice†.2020

    • Author(s)
      Miyata H, Abbasi F, Visconti PE, Ikawa M.
    • Journal Title

      Biol Reprod.

      Volume: 103 Issue: 5 Pages: 912-914

    • DOI

      10.1093/biolre/ioaa161

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility2020

    • Author(s)
      Oura Seiya、Kazi Samina、Savolainen Audrey、Nozawa Kaori、Castaneda Julio、Yu Zhifeng、Miyata Haruhiko、Matzuk Ryan M.、Hansen Jan N.、Wachten Dagmar、Matzuk Martin M.、Prunskaite-Hyyrylainen Renata
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 8 Pages: e1008954-e1008954

    • DOI

      10.1371/journal.pgen.1008954

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility2020

    • Author(s)
      Liu Chunyu、Miyata Haruhiko、Gao Yang、Sha Yanwei、Tang Shuyan、Xu Zoulan、、、Wu Huan、Dulioust Emmanuel、Tian Shixiong、Shimada Keisuke、Cong Jiangshan、、、Aminata、Zhang Feng、Ikawa Masahito
    • Journal Title

      The American Journal of Human Genetics

      Volume: 107 Issue: 2 Pages: 330-341

    • DOI

      10.1016/j.ajhg.2020.06.004

    • Related Report
      2020 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of the sperm flagellar axoneme using gene-modified mice2020

    • Author(s)
      Miyata H, Morohoshi A, Ikawa M.
    • Journal Title

      Experimental Animals

      Volume: 69 Issue: 4 Pages: 374-381

    • DOI

      10.1538/expanim.20-0064

    • NAID

      130007938660

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2020 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
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male mice†.2020

    • Author(s)
      Nozawa K, Zhang Q, Miyata H, Devlin DJ, Yu Z, Oura S, Koyano T, Matsuyama M, Ikawa M, Matzuk MM.
    • Journal Title

      Biol Reprod.

      Volume: 103 Issue: 2 Pages: 244-253

    • DOI

      10.1093/biolre/ioaa040

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Testis‐enriched kinesin KIF9 is important for progressive motility in mouse spermatozoa2020

    • Author(s)
      Miyata Haruhiko、Shimada Keisuke、Morohoshi Akane、Oura Seiya、Matsumura Takafumi、Xu Zoulan、Oyama Yuki、Ikawa Masahito
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 4 Pages: 5389-5400

    • DOI

      10.1096/fj.201902755r

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice2020

    • Author(s)
      Morohoshi Akane、Miyata Haruhiko、Shimada Keisuke、Nozawa Kaori、Matsumura Takafumi、Yanase Ryuji、Shiba Kogiku、Inaba Kazuo、Ikawa Masahito
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 1 Pages: 1-21

    • DOI

      10.1371/journal.pgen.1008585

    • NAID

      120007159540

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycerol kinase 2 is essential for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during mouse spermatogenesis2019

    • Author(s)
      Shimada K, Kato H, Miyata H, Ikawa M.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 65 Issue: 2 Pages: 155-162

    • DOI

      10.1262/jrd.2018-136

    • NAID

      130007630929

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
  • [Journal Article] Chimeric analysis with newly established EGFP/DsRed2-tagged ES cells identify HYDIN as essential for spermiogenesis in mice2019

    • Author(s)
      Oura Seiya、Miyata Haruhiko、Noda Taichi、Shimada Keisuke、Matsumura Takafumi、Morohoshi Akane、Isotani Ayako、Ikawa Masahito
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 1 Pages: 25-34

    • DOI

      10.1538/expanim.18-0071

    • NAID

      130007604401

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RSPH6A is required for sperm flagellum formation and male fertility in mice2018

    • Author(s)
      Abbasi Ferheen、Miyata Haruhiko、Shimada Keisuke、Morohoshi Akane、Nozawa Kaori、Matsumura Takafumi、Xu Zoulan、Pratiwi Putri、Ikawa Masahito
    • Journal Title

      Journal of Cell Science

      Volume: 131 Pages: 1-11

    • DOI

      10.1242/jcs.221648

    • NAID

      120006957445

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models2018

    • Author(s)
      fujihara Y, Miyata H, Ikawa M.
    • Journal Title

      Experimental Animals

      Volume: 67 Issue: 2 Pages: 91-104

    • DOI

      10.1538/expanim.17-0153

    • NAID

      130006733631

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa.2017

    • Author(s)
      Castaneda JM, Hua R, Miyata H, Oji A, Guo Y, Cheng Y, Zhou T, Guo X, Cui Y, Shen B, Wang Z, Hu Z, Zhou Z, Sha J, Prunskaite-Hyyrylainen R , Yu Z, Ramirez-Solis R, Ikawa M, Matzuk MM and Liu M
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 114(27) Issue: 27

    • DOI

      10.1073/pnas.1621279114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Revolutionizing male fertility factor research in mice by using the genome editing tool CRISPR/Cas9.2017

    • Author(s)
      Abbasi F, Miyata H, Ikawa M.
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 17(1) Issue: 1 Pages: 3-10

    • DOI

      10.1002/rmb2.12067

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] KIF9はマウス精子運動性の制御に重要である2020

    • Author(s)
      宮田治彦, 嶋田圭祐, 諸星茜, 大浦聖矢, 松村貴史, Zoulan Xu, 大山裕貴, 伊川正人
    • Organizer
      日本アンドロロジー学会 第39回学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] DRC7 is required for sperm flagellum formation and male fertility in mice2019

    • Author(s)
      宮田治彦, 諸星茜, 嶋田圭祐, 野澤香織, 松村貴史, 伊川正人
    • Organizer
      52nd Annual Meeting of the Society for the Study of Reproduction
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゲノム編集技術を用いた精子機能の解析2019

    • Author(s)
      宮田治彦
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] マウスRSPH6Aは精子鞭毛の形成と生殖能力に必須である2019

    • Author(s)
      宮田治彦, Ferheen Abbasi, 嶋田圭祐, 諸星茜, 野澤香織, 松村貴史, Zoulan Xu, Putri Pratiwi, 伊川正人
    • Organizer
      日本アンドロロジー学会第38回学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CRISPR/Cas9システムを駆使した精子機能の解析2018

    • Author(s)
      宮田治彦、Julio M Castaneda、大浦聖矢、伊川正人
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] RSPH6A is essential for sperm flagellum formation and male fertility in mice2018

    • Author(s)
      宮田治彦, Ferheen Abbasi, 嶋田圭祐, 諸星茜, 野澤香織, 松村貴史, 伊川正人
    • Organizer
      51st Annual Meeting of the Society for the Study of Reproduction
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウスRSPH6Aは精子鞭毛の形成と生殖能力に必須である2018

    • Author(s)
      宮田治彦, Ferheen Abbasi, 嶋田圭祐, 松村貴史, 諸星茜, 伊川正人
    • Organizer
      第65回日本実験動物学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CABYR is essential for fibrous sheath integrity and progressive motility in mouse spermatozoa2017

    • Author(s)
      Haruhiko Miyata, Samantha A.M. Young, Yuhkoh Satouh, R. John Aitken, Mark A. Baker, Masahito Ikawa
    • Organizer
      Fertilization & Activation of Development (Gordon Research Conference)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sperm motility and its competency for mammalian fertilization2017

    • Author(s)
      Haruhiko Miyata, Masahito Ikawa
    • Organizer
      50th Annual Meeting of the Society for the Study of Reproduction
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] IZUMO1の細胞内領域はマウスの生殖能力に必須ではない2017

    • Author(s)
      宮田治彦、Samantha A.M. Young、佐藤裕公、武藤真長、Martin R. Larsen、R. John Aitken、Mark A. Baker、伊川正人
    • Organizer
      第64回日本実験動物学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゲノム編集技術を用いた精子機能の解析2017

    • Author(s)
      宮田治彦
    • Organizer
      安全性評価研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] ゲノム編集技術を用いた精子機能の解析 (谷本学校 毒性質問箱)2018

    • Author(s)
      諸星茜,宮田治彦,伊川正人
    • Total Pages
      100
    • Publisher
      サイエンティスト社
    • Related Report
      2018 Annual Research Report
  • [Book] 宮田治彦, 伊川正人2017

    • Author(s)
      ゲノム編集と生殖工学への応用 (臨床婦人科産科)
    • Total Pages
      95
    • Publisher
      医学書院
    • Related Report
      2017 Annual Research Report
  • [Remarks] 遺伝子機能解析分野 HP

    • URL

      https://egr.biken.osaka-u.ac.jp/achievement/original_articles

    • Related Report
      2020 Annual Research Report
  • [Remarks] 大阪大学微生物病研究所遺伝子機能解析分野HP

    • URL

      http://www.egr.biken.osaka-u.ac.jp/information/results/index.html

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-23  

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