Development of human antibody producing mice with human immune systems

开发具有人类免疫系统的产生人类抗体的小鼠

• 批准号: 22700458
• 负责人: ITO Ryoji
• 金额: $ 2.58万
• 依托单位: Central Institute for Experimental Animals
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700458/
• 关键词: ヒト化マウス; 疾患モデル; ヒト抗体; アレルギー; ヒト抗体産生; ヒト遺伝子導入NOGマウス; ヒト型抗体

The purpose in this research is producing humanized mice reconstituted with human immune system. We obtained 2 strains of human gene transgenic (Tg) mice (HLA-DR4 Tg, IL-3/GM-CSF Tg), and human HSCs were transferred into them to analyze human immune responses in vivo. HLA-DR4 Tg mice showed the production of an antigen specific human IgG antibody and promotion of T cell activity. Meanwhile, differentiation of human mast cells and basophils were increased in hIL-3/GM Tg mice, and they could induce passive allergic response in vivo. Therefore, these humanized Tg mice may contribute to medical research such as the pre-clinical study on the development of new drug.

本研究的目的是培育具有人体免疫系统的人源化小鼠。我们获得了2株人基因转基因（Tg）小鼠（HLA-DR4 Tg, IL-3/GM-CSF Tg），并将人造血干细胞转移到它们体内，分析人体内的免疫反应。HLA-DR4 Tg小鼠显示出抗原特异性人IgG抗体的产生和T细胞活性的促进。同时，hIL-3/GM Tg小鼠的人肥大细胞和嗜碱性细胞分化增加，在体内可诱导被动过敏反应。因此，这些人源化Tg小鼠可能有助于医学研究，如新药开发的临床前研究。

项目成果

Efficient Xenoengraftment in Severe Immunodeficient NOD/Shi-scid IL2rγnull Mice Is Attributed to a Lack of CD11c+B220+CD122+ Cells

• DOI: 10.4049/jimmunol.1200820
• 发表时间: 2012-11-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Ito, Ryoji;Katano, Ikumi;Ito, Mamoru
• 通讯作者: Ito, Mamoru

Immunodeficient NOD-scid IL-2Rγnull Mice Do Not Display T and B Cell Leakiness

• DOI: 10.1538/expanim.60.181
• 发表时间: 2011-04-01
• 期刊: EXPERIMENTAL ANIMALS
• 影响因子: 2.4
• 作者: Katano, Ikumi;Ito, Ryoji;Ito, Mamoru
• 通讯作者: Ito, Mamoru

Functional maturation of human myeloid cells in a NOD/SCID/IL2rγnull (NOG) transgenic humanized mouse strain expressing human IL-3 and GM-CSF

表达人 IL-3 和 GM-CSF 的 NOD/SCID/IL2rγnull (NOG) 转基因人源化小鼠品系中人骨髓细胞的功能成熟

• 发表时间: 2012
• 作者: 東岸任弘;青枝大貴;八木正典;有末伸子;片貝祐子;保富康宏;甲斐知恵子;石井健;堀井俊宏;伊藤亮治
• 通讯作者: 伊藤亮治

Development of a human allergy model animal using novel NOG transgenic humanized mouse strain expressing human IL-3 and GM-CSF

使用表达人IL-3和GM-CSF的新型NOG转基因人源化小鼠品系开发人类过敏模型动物

• 发表时间: 2012
• 作者: Katano I;Ito R;Eto T;Aiso S;Ito M;伊藤亮治
• 通讯作者: 伊藤亮治

Interferon-gamma produced by IKDC has a crucial role in suppression of xeno-GVHD in NOG mice

IKDC 产生的干扰素-γ 在抑制 NOG 小鼠异种 GVHD 中具有至关重要的作用

• 发表时间: 2010
• 作者: Takahiro Tougan;Taiki Aoshi;Masanori Yagi;Cevayir Coban;Nobuko Arisue;Yuko Katakai;Yasuhiro Yasutomi;Chieko Kai;Ken J.Ishii;Toshihiro Horii;伊藤亮治;伊藤亮治
• 通讯作者: 伊藤亮治