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Establishment of a strain of F8 gene-targeted pigs (hemophilia-A pigs) by xenografting of fetal testicular tissue from neonatally moribund cloned pigs

Research Project

Project/Area Number 26292171
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionNational Agriculture and Food Research Organization (2016)
National Institute of Agrobiological Sciences (2014-2015)

Principal Investigator

KANEKO Hiroyuki  国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門 動物機能利用研究領域, ユニット長 (60343993)

Co-Investigator(Kenkyū-buntansha) 菊地 和弘  国立研究開発法人農業生物資源研究所, 動物発生分化研究ユニット, 上級研究員 (20360456)
中井 美智子  国立研究開発法人農業生物資源研究所, 医用モデルブタ研究開発ユニット, 任期付研究員 (30442825)
大西 彰  日本大学, 生物資源科学部, 教授 (30414890)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywords血友病モデルブタ / 精巣異種間移植 / 超低温保存 / 系統樹立 / 精祖細胞 / 異種間移植
Outline of Final Research Achievements

Our institute has developed a porcine model of hemophilia-A (hemophilia-A pig) by nuclear transfer cloning of fetal fibroblasts after disruption of the X-linked coagulation factor VIII (F8) gene. As a recessive disease, heterozygous female clones were expected to be asymptomatic, but died of severe bleeding as well as hemizygous male clones, thus making it impossible to obtain progeny of the hemophilia-A pigs. In this study, we tried to establish a strain of hemophilia-A pigs utilizing sperm recovered from testicular tissue of fetal hemizygous clones that had been grafted into nude mice. Two heterozygous pigs were generated: the pigs were asymptomatic and then delivered 5 hemizygous and 4 heterozygous piglets. Thus, testicular xenografting provides an opportunity to generate offspring from fetal hemizygous clones. Such heterozygous pigs avoid the discrepancy between genotype and phenotype in terms of F8, and will distribute progeny for the development of new therapeutics.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(9 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results) Presentation (5 results)

  • [Journal Article] Production of sperm from porcine fetal testicular tissue after cryopreservation and grafting into nude mice2017

    • Author(s)
      Hiroyuki Kaneko, Kazuhiro Kikuchi, Nguyen Thi Men, Michiko Nakai, Junko Noguchi, Naomi Kashiwazaki, Junya Ito
    • Journal Title

      Theriogenology

      Volume: 91 Pages: 154-162

    • DOI

      10.1016/j.theriogenology.2016.12.036

    • NAID

      130007023577

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Growth and fertilization of porcine fetal oocytes grafted under the renal capsules of nude mice2016

    • Author(s)
      Hiroyuki Kaneko, Kazuhiro Kikuchi, Junko Noguchi
    • Journal Title

      Theriogenology

      Volume: 86 Pages: 1740-1748

    • DOI

      10.1016/j.theriogenology.2016.05.031

    • NAID

      130005492043

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Contribution of in vitro systems to preservation and utilization of porcine genetic resources2016

    • Author(s)
      Kazuhiro Kikuchi, Hiroyuki Kaneko, Michiko Nakai, Tamas Somfai, Naomi Kashiwazaki, Takashi Nagai
    • Journal Title

      Theriogenology

      Volume: 86 Pages: 170-175

    • DOI

      10.1016/j.theriogenology.2016.04.029

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Normal reproductive development of pigs produced using sperm retrieved from immature testicular tissue cryopreserved and grafted into nude mice2014

    • Author(s)
      Kaneko H, Kikuchi K, Kashiwazaki N. ほか
    • Journal Title

      Theriogenology

      Volume: 15 Pages: 325-331

    • DOI

      10.1016/j.theriogenology.2014.04.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 超低温保存したブタ胎子精巣の異種間移植による精子の発生2016

    • Author(s)
      金子浩之、菊地和弘、Nguyen Thi Men、中井美智子、野口純子、伊藤潤哉、柏崎直巳
    • Organizer
      日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県・相模原市)
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] Production of Piglets Using Sperm Retrieved from Host Mice Harboring Fetal Testicular Tissue of F8 Gene-Targeted Hemophilia A Pigs2016

    • Author(s)
      Hiroyuki Kaneko, Kazuhiro Kikuchi, Michiko Nakai, Daiichiro Fuchimoto, Shunichi Suzuki, Shoichiro Senbon, Akira Onishi
    • Organizer
      Society for the Study of reproduction, 2016
    • Place of Presentation
      Sheraton San Diego Hotel & Marina, USA
    • Year and Date
      2016-07-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Production of Piglets Using Sperm Retrieved from Host Mice Harboring Fetal Testicular Tissue of F8 Gene- Targeted Hemophilia A Pigs2016

    • Author(s)
      Hiroyuki Kaneko, Kazuhiro Kikuchi, Michiko Nakai, Daiichiro Fuchimoto, Shunichi Suzuki, Sembon Shouichiro, Junko Noguchi, Akira Onishi
    • Organizer
      Society for the study of reproduction
    • Place of Presentation
      San Diego (アメリカ合衆国)
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 異種間移植によるブタ胎子卵巣の発育と卵の受精能2015

    • Author(s)
      金子浩之、菊地和弘、野口純子
    • Organizer
      第108回日本繁殖生物学会
    • Place of Presentation
      宮崎大学
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Recovery of porcine sperm from fetal testicular tissue xenografted into nude mice2014

    • Author(s)
      Kikuchi K, Noguchi J, Kaneko H
    • Organizer
      World Congress of Reproductive Biology 2014
    • Place of Presentation
      スコットランド
    • Year and Date
      2014-09-02 – 2014-09-04
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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