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Development of highly immunodeficient mice by regulating innate immune systems

Research Project

Project/Area Number 18H02368
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Takahashi Takeshi  公益財団法人実験動物中央研究所, 実験動物基礎研究部, 部長 (80335215)

Co-Investigator(Kenkyū-buntansha) 玉井 恵一  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん幹細胞研究部, 部長 (40509262)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsimmunodeficient mice / innate immunity / RBC / FcR / antibody / ADCC / tumor immunology / immunocheckpoint / ヒト化マウス / Fc受容体 / 自然免疫 / マクロファージ / 抗体医薬 / PDX
Outline of Final Research Achievements

A severe immunodeficient NOG mouse allow the engraftment of human living cells or tissues due to the lack of endogenous immune systems. Nevertheless, all the human cells(e.g. RBC)are not engrafted. A reason is considered rejection by mouse innate immune systems. To elucidate the mechanisms and to increase the degree of immunodeficiency, we established NOG-C3KO and NOG-FcRKO mice. In NOG-C3KO, the extension of the survival of transfused human RBC was detected. Accompanied with GdCl3, they persisted for nearly one month. In NOG-FcRKO mice, overall engraftment of human cells was enhanced compared to NOG mice. In addition, they lack the antibody dependent cellular cytotoxicity (ADCC) by mouse innate cells. This enabled the specific detection of biological activities by therapeutic antibodies.

Academic Significance and Societal Importance of the Research Achievements

本研究ではマウス内在性の免疫系によるヒト細胞の認識機構を明らかにするため、マウスC3とFcRを欠損するマウスを作製した。NOG-C3KOマウスではヒト赤血球の生着が容易になり、将来のマラリア感染研究に役立つものと考えられる。NOG-FcRKOマウスではヒト細胞の生着が向上するともに、さまざまな抗体治療薬の生体内での活性検定が容易になり、新薬開発に有用なモデルが樹立できた。

Report

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

    (15 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Singapore Immunology Network(シンガポール)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models2021

    • Author(s)
      Mori A, Murata S, Tashiro N, Tadokoro T, Okamoto S, Otsuka R, Wada H, Murata T, Takahashi T, Seino KI, Taniguchi H.
    • Journal Title

      Cells

      Volume: 10 Issue: 2 Pages: 476-476

    • DOI

      10.3390/cells10020476

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bovine β-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/hGM-CSF transgenic mice2020

    • Author(s)
      Ito Ryoji、Katano Ikumi、Otsuka Iyo、Takahashi Takeshi、Suemizu Hiroshi、Ito Mamoru、Simons Peter J
    • Journal Title

      International Immunology

      Volume: 33 Issue: 3 Pages: 183-189

    • DOI

      10.1093/intimm/dxaa067

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Improved Detection of in vivo Human NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Using a Novel NOG-FcγR-Deficient Human IL-15 Transgenic Mouse2020

    • Author(s)
      Katano Ikumi、Ito Ryoji、Kawai Kenji、Takahashi Takeshi
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 1-9

    • DOI

      10.3389/fimmu.2020.532684

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway2020

    • Author(s)
      Murai Kazuhiro、Hikita Hayato、Kai Yugo、Kondo Yasuteru、Fukuoka Makoto、Fukutomi Keisuke、Doi Akira、Yamai Takuo、Nakabori Tasuku、Fukuda Ryo、Takahashi Takeshi、Miyakawa Kei、Suemizu Hiroshi、Ryo Akihide、Yamada Ryoko、Kodama Takahiro、Sakamori Ryotaro、Tatsumi Tomohide、Takehara Tetsuo
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 941-941

    • DOI

      10.1038/s41598-020-57603-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent Advances in Allergy Research Using Humanized Mice2019

    • Author(s)
      Ito Ryoji、Maruoka Shuichiro、Gon Yasuhiro、Katano Ikumi、Takahashi Takeshi、Ito Mamoru、Izuhara Kenji、Nunomura Satoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 11 Pages: 2740-2740

    • DOI

      10.3390/ijms20112740

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exacerbation of pathogenic Th17-cell-mediated cutaneous graft-versus-host-disease in human IL-1β and IL-23 transgenic humanized mice.2019

    • Author(s)
      Ito R, Katano I, Otsuka I, Hanazawa A, Takahashi T, Kawai K, Yagoto M, Goto M, Ogura T, Takahashi R, Ito M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 516 Issue: 2 Pages: 480-485

    • DOI

      10.1016/j.bbrc.2019.06.094

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 免疫系ヒト化マウスを用いた抗体医薬品評価2020

    • Author(s)
      高橋武司
    • Organizer
      第27回HAB研究機構学術年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Development of human neutrophils in hG-CSF knockin NOG mouse transferred with human HSC2019

    • Author(s)
      Ito R, Katano I, Takahashi T, Goto M, Takahashi R, Ito M
    • Organizer
      103rd American Association of Immunology
    • Related Report
      2019 Annual Research Report
  • [Presentation] 抗体受容体欠損型NOG-FcRKOマウスを用いた抗PD-1抗体の機能評価モデル2019

    • Author(s)
      片野いくみ 花澤麻美 大塚伊代 伊藤亮治 位高美香 川井健司 高橋武司
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Beta-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/GM-CSF Tg mice2019

    • Author(s)
      Ito R, Katano I, Otsuka I, Takahashi T, Ito M, and Simons PJ
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Specific detection of human NK cell mediated in vivo ADCC in FcgR-deficient NOG-human IL-15 transgenic mice2019

    • Author(s)
      Ikumi Katano*, Asami Hanazawa, Ryoji Ito, Mamoru Ito, Takeshi Takahashi
    • Organizer
      AACR
    • Related Report
      2018 Annual Research Report
  • [Presentation] Specific detection of human NK cell mediated in vivo ADCC in FcgR-deficient NOG-human IL-15 transgenic mice2018

    • Author(s)
      片野いくみ、 花澤麻美、伊藤亮治、伊藤守、高橋武司
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Modification of human hematopoiesis in novel NOG strain2018

    • Author(s)
      高橋武司
    • Organizer
      International Symposium of Humanized mouse models
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] 免疫不全マウス2018

    • Inventor(s)
      高橋武司
    • Industrial Property Rights Holder
      公益財団法人実験動物中央研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-181930
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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

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