Studies on the development of allergy treatment using gene-knockout mice.

使用基因敲除小鼠进行过敏治疗的研究进展。

• 批准号: 06650918
• 负责人: OHMORI Hitoshi
• 金额: $ 1.34万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06650918/
• 关键词: gene targeting; Fc gamma receptor; gene-knockout mouse; allergy; anaphylaxy; IgG immune complex; B cells; mast cells; Fcガンマレセプター; 抗体; 遺伝子ノックアウト; ES細胞; 変異マウス; IgE抗体; リンパ球; IgG Fc受容体; クラススイッチ; 遺伝子ターゲッティング; ノックアウトマウス

The present research project is unique in that we attempted to develop technologies for the treatment of allergic diseases by focusing the role of Fc gamma receptor II (FcgammaRII). For this purpose, we established FcgammaRII-deficient mice by gene-targeting as follows. Targeting vector. A.2.65-kb BamHI fragment containing S1 and EC1 exon was replaced by a neo-resistant gene cassette. Homologous J1 ES cell recombinants were obtained at a frequency of 10.4%. Offsprings of heterozygous intercrosses were examined for the gene knockout by Southern blot of genomic DNA isolated from tail tips. It was found that one out of four offsprings possessed the homozygous disrupted gene in accordance with Mendelian frequency. Lack of FcgammaRII protein was confirmed on B cells, macrophages and mast cells by flow cytometry. Sensitivities of this animal to various allergic stimuli are being investigated.

本研究项目的独特之处在于，我们试图通过关注Fc γ受体II（Fc γ RII）的作用来开发治疗过敏性疾病的技术。为此目的，我们通过如下基因靶向建立了Fc γ RII缺陷型小鼠。目标载体A.2.65-kb BamHI片段含有S1和EC 1外显子，被新抗性基因盒取代。重组子的获得频率为10.4%。通过Southern杂交检测杂合杂交后代的基因敲除情况。结果发现，四个后代中有一个具有与孟德尔频率一致的纯合破坏基因。通过流式细胞术证实在B细胞、巨噬细胞和肥大细胞上缺乏Fc γ RII蛋白。正在研究该动物对各种过敏刺激的敏感性。

项目成果

Naoki Hase, Toshiyuki Takai, Masaki Hikida and Hitoshi Ohmori: "Predominant suppression of anti-TNP IgE response in mice by monoclonal anti-TNP IgG1 antibody. Characterization of its mode of action by in vivo and in vitro studies." Int.J.Immunopharmacol.V

Naoki Hase、Toshiyuki Takai、Masaki Hikida 和 Hitoshi Ohmori：“单克隆抗 TNP IgG1 抗体显着抑制小鼠中的抗 TNP IgE 反应。通过体内和体外研究表征其作用模式。”

T.Takai,H.Ohmori et al.: "Augmented humoral and anaphylactic responses in FcγR II-deficient mice." Nature. 379. 346-349 (1996)

T. Takai、H. Ohmori 等人：“FcγR II 缺陷小鼠的体液和过敏反应增强。” Nature 379. 346-349 (1996)

T, Takai, H. Ohmori et al.: "Augmented humoral and anaphylactic responses in FcγRII-deficient mice." Nature. 378. 346-349 (1996)

T, Takai, H. Ohmori 等人：“FcγRII 缺陷小鼠的体液和过敏反应增强。” Nature 378. 346-349 (1996)

N, Hase, H, Ohmori et al.: "Predominant suppression of anti TNP igE response in mice by monoclonal anti-TNP IgG1 antibody" Int. J. Immunopharmacol.16. 787-794 (1994)

N、Hase、H、Ohmori 等人：“单克隆抗 TNP IgG1 抗体对小鼠中抗 TNP igE 反应的显着抑制” Int。

Toshiyuki Takai, Masao Ono, Masaki Hikida, Hitoshi Ohmori and Jeffery Ravetch: "Augmented humoral and anaphylactic responses in FcgammaRII-deficient mice." Nature. Vol.378. 346-349 (1996)

Toshiyuki Takai、Masao Ono、Masaki Hikida、Hitoshi Ohmori 和 Jeffery Ravetch：“FcgammaRII 缺陷小鼠的体液和过敏反应增强。”