PRODUCTION OF IGE RECEPTOR-DEFICIENT MICE BY HOMOLOGOUS RECOMBINATION

通过同源重组生产 IGE 受体缺陷型小鼠

• 批准号: 3746645
• 负责人: J P KINET
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746645
• 关键词: antibody receptor; genetic recombination; genetically modified animals; hypersensitivity; immunoglobulin E; laboratory mouse; mast cell; receptor expression

Mast cells and basophils, which are activated by immunoglobulin E (IgE) and allergen, play a prominent role in anaphylaxis. However, they express at least three types of IgE receptors: the high affinity IgE receptor (Fc(epsilon)RI), and the two low affinity IgG receptors (Fc(gamma)RII and Fc(gamma)RIII) also capable of binding IgE. The relative contribution of these, and possibly other receptors such as CD23/Fc(epsilon)RII and Mac- 2, to the genesis of in vivo anaphylaxis is still unclear. To address this question, we have generated mice deficient mice with a disrupted Fc(epsilon)RI alpha chain gene. This defect results in complete suppression of the cell surface expression of Fc(epsilon)RI. These mice appear normal and express a normal number of mast cells, but they are resistant to cutaneous and systemic anaphylaxis. These data demonstrate that Fc(epsilon)RI is necessary for the initiation of IgE-dependent anaphylactic reactions. Therefore, interfering with its function should be an effective means of treating allergy, regardless of the allergen specificity. We are also in the process of generating mice with a disrupted Fc(epsilon)RI beta chain gene. Since the beta chain not only associate with Fc(epsilon)RI but also with Fc(gamma)RIII, these mice should allow us to analyze the contribution of the beta chain in Fc(gamma)RIII-related cell activation.

肥大细胞和嗜碱性粒细胞，由免疫球蛋白E（IgE）激活 和过敏原，在过敏反应中起着重要作用。然而，他们表示， 至少三种类型的IgE受体：高亲和力IgE受体 （Fc（γ）RI）和两种低亲和力IgG受体（Fc（γ）RII和Fc（γ）RI）。 Fc（gamma）RIII）也能够结合IgE。的相对贡献 这些，以及可能的其他受体，如CD 23/Fc（CD 23）RII和Mac- 2、致体内过敏反应的发生机制尚不清楚。解决 这个问题，我们已经产生了小鼠缺陷小鼠与破坏 Fc（α）RI α链基因。该缺陷导致完全 抑制Fc（γ）RI的细胞表面表达。这些小鼠 表现正常并表达正常数量的肥大细胞，但它们 抗皮肤和全身过敏反应。这些数据证明 Fc（γ）RI是启动IgE依赖性 过敏反应因此，干扰其功能应 是治疗过敏的有效手段，无论过敏原是什么， 的特异性 我们也在生产一种被破坏的小鼠， Fc（α）RI β链基因。因为贝塔链不仅 与Fc（γ）RI和Fc（γ）RIII，这些小鼠应允许 我们分析了β链在Fc（γ）RIII相关的 细胞激活