Development of highly immunodeficient mice by regulating innate immune systems

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02368
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Central 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
• Keywords: immunodeficient mice / innate immunity / RBC / FcR / antibody / ADCC / tumor immunology / immunocheckpoint

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.

Free Research Field

免疫学

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。