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Development of MODY5 model mouse using blastocyst complementation

Research Project

Project/Area Number 18K06044
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

Hashimoto Haruo  公益財団法人実験動物中央研究所, 教育・研修室, 研究員 (30353478)

Co-Investigator(Kenkyū-buntansha) 外丸 祐介  広島大学, 自然科学研究支援開発センター, 教授 (90309352)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords胚盤胞補完法 / マウス / MODY2 / MODY5 / ES細胞 / 糖尿病 / インスリン / 腎疾患 / HNF-1β / shRNA / 腎臓 / 膵臓
Outline of Final Research Achievements

The purpose of this study was to generate a model mouse of Maturity-onset diabetes mellitus of the young type5; MODY5), which is an intractable disease, by using the blastocyst complementation method.Therefore, this time, ES cells (shRNA-ES cells) expressing shRNA for the HNF-1β gene were injected into blastocyst stage eggs of pancreatic and kidney-deficient mice to prepare a chimera.
Asthe results, the chimeric mice produced showed diabetes. From these results, it was shown that the blastocyst complementation method using diseased ES / iPS cells (donor cells) reflects the characteristics of donor cells in the pancreas.

Academic Significance and Societal Importance of the Research Achievements

疾患ES/iPS細胞(ドナー細胞)を用いた胚盤胞補完法は、膵臓ではドナー細胞の特性を反映することが示された。この結果は、ヒトの疾患iPS細胞を用いた場合でも、マウスで個人の膵臓疾患の特性を再現できるものと期待される。
今回、腎臓ではキメラが作製できなかったが、キメラ作製効率の向上により様々な臓器でのヒト化マウスを可能にすると思われる。

Report

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

    (13 results)

All 2020 2019 2018 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Expression of MCP-1 in white adipose tissues induce the resistin-hypersecretion in type 2 diabetes.2020

    • Author(s)
      Haruo HASHIMOTO, Tomoo ETO, Kenji KAWAI, Toshio AKIMOTO, Kyoji HIOKI
    • Journal Title

      Obesity Medicine

      Volume: 20 Pages: 100286-100290

    • DOI

      10.1016/j.obmed.2020.100286

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ビニールアイソレータへの応用を目指した宇宙服用ファスナーの気密性に関する検討2019

    • Author(s)
      斎藤宗雄, 今井都泰, 冨澤政史, 橋本晴夫, 日置恭司
    • Journal Title

      実験動物技術

      Volume: 54 Pages: 7-11

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of blastocyst complementation technology without contributions to gametes and the brain2019

    • Author(s)
      Haruo HASHIMOTO, Tomoo ETO, Masafumi YAMAMOTO, Mika YAGOTO, Motohito GOTO, Takahiro KAGAWA, Keisuke KOJIMA, Kenji KAWAI, Toshio AKIMOTO, Ri-ichi TAKAHASHI
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 3 Pages: 361-370

    • DOI

      10.1538/expanim.18-0173

    • NAID

      130007689918

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adiponectin deficiency-induced diabetes increases TNFα and FFA via downregulation of PPARα2018

    • Author(s)
      Haruo HASHIMOTO,Masafumi YAMAMOTO, Emika SUGIURA, Hayato ABE, Takahiro KAGAWA, Ri-ichi TAKAHASHI, Toshio AKIMOTO, Hiroshi SUEMIZU.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 4 Pages: 662-666

    • DOI

      10.1292/jvms.17-0641

    • NAID

      130006708371

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sox17 is essential for proper formation of the marginal zone of extraembryonic endoderm adjacent to a developing mouse placental disk.2018

    • Author(s)
      Igarashi H, Uemura, M, Hiramatsu R, Hiramatsu R, Segami S, Pattarapanawan M, Hirate Y, Yoshimura Y, Hashimoto H, Higashiyama H, Sumitomo H, Kurohmaru M, Saijoh Y, Suemizu H, Kanai-Azuma M, Kanai Y.
    • Journal Title

      Biol Reprod

      Volume: - Issue: 3 Pages: 578-589

    • DOI

      10.1093/biolre/ioy079

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 炭酸ガスを用いた減衰法による飼育ケージの換気回数の測定.2018

    • Author(s)
      斎藤宗雄, 今井都秦, 冨澤政史, 橋本晴夫, 日置恭司.
    • Journal Title

      実験動物技術

      Volume: 53 (2) Pages: 67-74

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 集塵性能に優れた新しいビニールアイソレータ用エアフィルター材の開発及び従前フィルターとの比較.2018

    • Author(s)
      斎藤宗雄, 今井都秦, 冨澤政史, 橋本晴夫, 日置恭司.
    • Journal Title

      実験動物技術

      Volume: 53 (2) Pages: 75-82

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 発光レポーターを用いた移殖胚選抜によるトランスジェニックマーモセット作製の効率化2020

    • Author(s)
      高橋司、佐藤人美、江藤智生、橋本晴夫、梅山一大、長嶋比呂志、佐々木 えりか
    • Organizer
      第8回 日本マーモセット研究会大会(シーサイドホテル舞子ビラ神戸)
    • Related Report
      2019 Research-status Report
  • [Presentation] 「動物実験技術者養成講座」15年間の総括2019

    • Author(s)
      冨澤政史、橋本晴夫、町田一彦、伊藤豊志雄、日置恭司、横山峯介
    • Organizer
      第66回日本実験動物学会総会(福岡国際会議場/福岡県)
    • Related Report
      2019 Research-status Report
  • [Presentation] 「動物実験」から「In vivo実験医学」へ-実中研が新たに展開する教育研修プログラムの紹介-2019

    • Author(s)
      橋本晴夫、冨澤政史、日置恭司、伊藤豊志雄、横山峯介
    • Organizer
      第53回日本実験動物技術者協会総会 (松山市総合コミュニティセンター/愛媛県).
    • Related Report
      2019 Research-status Report
  • [Presentation] アディポネクチン欠損によるPPARαの発現低下を介したTNFαの増加2018

    • Author(s)
      橋本晴夫、山本真史、杉浦恵美香、阿倍隼人、香川貴洋、後藤元人、高橋利一、秋元敏雄、末水洋志
    • Organizer
      第65回日本実験動物学会総会(富山県民会館)
    • Related Report
      2018 Research-status Report
  • [Remarks] 第67回日本実験動物学会総会 最優秀論文賞

    • URL

      https://jalas67.org/program.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 実験動物中央研究所ホームページ

    • URL

      https://www.ciea.or.jp/introduction/animal_resources/development.html

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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