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精子幹細胞の増殖機構の解明とその発生工学への応用

Research Project

Project/Area Number 15080205
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

篠原 隆司  Kyoto University, 医学研究科, 教授 (30322770)

Project Period (FY) 2003 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥83,100,000 (Direct Cost: ¥83,100,000)
Fiscal Year 2007: ¥22,200,000 (Direct Cost: ¥22,200,000)
Fiscal Year 2006: ¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 2005: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2004: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2003: ¥12,800,000 (Direct Cost: ¥12,800,000)
Keywords精子形成 / 幹細胞 / ノックアウト / オクルジン / アデノウイルス / 移植 / ゲノム / 遺伝子 / 分化 / バイオテクノロジー / 不妊 / 培養 / 精子幹細胞 / 精子 / 生殖細胞
Research Abstract

今年度は精子幹細胞を利用した新しい遺伝子導入法を報告した(Takehashi, et. al., Proc. Natl. Acad. Sci. USA.
2007).従来精子形成細胞はアデノウイルスには感染しないと考えられていたが、今回我々はアデノウイルスを試験管内で精子幹細胞株Germline Stem (GS)細胞に感染させることでアデノウイルスが生殖細胞に感染しうることを行うことを見いだした。この実験系においてアデノウイルスの感染したGS細胞から産仔を作成したところ、そのどの子孫にもアデノウイルス由来のDNAを見つけることができなかったことから、アデノウイルスは一過性にGS細胞において遺伝子発現したのち、GS細胞のゲノムに挿入されることなくGS細胞の分裂とともに消失したことが予想された。我々はこれまでにGS細胞への安定的な遺伝子改変方法を開発してきたが、今回のアデノウイルスを利用した一過性の遺伝子発現系はそれらの方法を補うものである。とくにアデノウイルスは感染効率が非常に高いので、多数の細胞に同時に遺伝子導入ができるという利点をもっており、今後の精子幹細胞の遺伝子操作に貴重な手法となる。
またさらに本年度我々は精単から樹立したmultipotent germline stem cell (mGS)細胞において相同組み替えを誘導し、オクルジン遺伝子を破壊個体の作成に成功した。オクルジン遺伝子をホモ個体として欠損したマウスを作成したところ、胚盤胞由来のembryonic stem (ES)細胞を用いて作成したオクルジン欠損個体と同じ表現形(男性不妊、慢性胃炎、骨粗鬆症など)を示した。この方法はES細胞、核移植、GS細胞に引き続く4番目の遺伝子破壊個体作成方法であり、今後mGS細胞をさまざまな動物種で樹立した場合に利用することが可能であることが期待される。

Report

(5 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006 2005 2004 Other

All Journal Article (18 results) (of which Peer Reviewed: 3 results) Patent(Industrial Property Rights) (1 results) Publications (6 results)

  • [Journal Article] Production of knockout mice by gene targeting in multipotent germline stem cells.2007

    • Author(s)
      Takehashi M., et. al.
    • Journal Title

      Dev. Biol. 312

      Pages: 344-352

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt mediates self-renewal division of mouse spermatogonial stem cells.2007

    • Author(s)
      Lee J, et. al.
    • Journal Title

      Development 134

      Pages: 1853-1859

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated gene delivery into mouse spermatogonial stem cells.2007

    • Author(s)
      Takehashi, et. al.
    • Journal Title

      PNAS 104

      Pages: 1596-2601

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of knockout mice by random and targeted mutagenesis in spermatogonial stem cells.2006

    • Author(s)
      kanatsu-shinohara et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 103

      Pages: 8018-8023

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clonal origin of germcell colonies after spermatogonial transplantation in mice2006

    • Author(s)
      kanatsu-shinohara et al.
    • Journal Title

      Biol.Reprod. 75

      Pages: 68-74

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Capillary morphogenesis gene(CMG)-1 is among the genes differentially expressed in mouse male germline stem and ES cells2006

    • Author(s)
      Fujino et al.
    • Journal Title

      Mol.Reprod.Dev. 73

      Pages: 955-966

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The germ of pluripotency2006

    • Author(s)
      kanatsu-shinohara et al.
    • Journal Title

      Nat.Biotechnol. 24

      Pages: 663-664

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rats produced by interspecies spermatogonial transplantation Oin mice in and microinsemination2006

    • Author(s)
      Shinohara et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 103

      Pages: 13624-13628

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Anchorage-independent growth of mouse male germline stem cells in vitro.2006

    • Author(s)
      Kanatsu-Shinohara M. et al.
    • Journal Title

      Biology of Reproduction 74,3

      Pages: 522-529

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Long-term culture of mouse male germline stem cells under serum-or feeder-free conditions.2006

    • Author(s)
      Kanatsu-Shinohara M. et al.
    • Journal Title

      Biology of Reproduction 72,4

      Pages: 985-991

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genetic and epigenetic properties of mouse male germline stem cells during long-term culture.2005

    • Author(s)
      Kanatsu-Shinohara M. et al.
    • Journal Title

      Development 132,18

      Pages: 4155-4163

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Germline niche transplantation restores fertility in infertile mice.2005

    • Author(s)
      Kanatsu-Shinohara M. et al.
    • Journal Title

      Human Reproduction 20,9

      Pages: 2376-2382

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Spermatogenesis from epiblast and primordial germ cells following transplantation into postnatal mouse testis.2005

    • Author(s)
      Chuma, S. et al.
    • Journal Title

      Development 132

      Pages: 117-122

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic selection of mouse male germline stem cells in vitro : Offspring from single stem cells.2005

    • Author(s)
      Kanatsu-Shinohara, M. et al.
    • Journal Title

      Biology of Reproduction 72

      Pages: 236-240

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Generation of pluripotent stem cells from neonatal mouse testis.2004

    • Author(s)
      Kanatsu-Shinohara, M. et al.
    • Journal Title

      Cell 119

      Pages: 1001-1012

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transgenic mouse produced by retroviral transduction of male germline stem cells in vivo.2004

    • Author(s)
      Kanatsu-Shinohara, M. et al.
    • Journal Title

      Biology of Reproduction 71

      Pages: 1202-1207

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of mouse spermatogonial stem cell self-renewing division by the pituitary gland.2004

    • Author(s)
      Kanatsu-Shinohara, M. et al.
    • Journal Title

      Biology of Reproduction 70

      Pages: 1731-1737

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CD9 is a surface marker on mouse and rat male germline stem cells.2004

    • Author(s)
      Kanatsu-Shinohara, M. et al.
    • Journal Title

      Biology of Reproduction 70

      Pages: 70-75

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 精巣細胞由来多能性幹細胞の製造方法2004

    • Inventor(s)
      篠原 隆司, 篠原 美都
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Number
      2004-101320
    • Filing Date
      2004-03-30
    • Related Report
      2004 Annual Research Report
  • [Publications] Shinohara, T., et al.: "Restoration of spermatogenesis in infertile mice by Sertoli cell transplantation"Biology of Reproduction. 68. 1064-1071 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanatsu-Shinohara M. et al.: "Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation"Biology of Reproduction. 68. 1801-1807 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanatsu-Shinohara, M. et al.: "Long-term proliferation in culture and germline transmission of mouse male germline stem cells"Biology of Reproduction. 69. 612-616 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshimoto, M. et al.: "Direct visualization of homing proliferation and quiescenece of transplanted hematopoietic cells in intact mouse organs : Indicative of the presence of niche"Exp.Hematol.. 31. 733-740 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanatsu-Shinohara, M. et al.: "Restoration of fertility in infertile mice by transplantation of cryopreserved male germline stem cells."Human Reproduction. 18. 2660-2667 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanatsu-Shinohara, M. et al.: "CD9 is a surface marker on mouse and rat male germline stem cells"Biology of Reproduction. 70. 70-75 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2018-03-28  

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