Genetically defined and selectively mast cell-deficient mouse model to unravel the immunological roles of mast cells

在许多生理和病理条件下，肥大细胞（MC）被认为在过敏性疾病之外发挥重要作用。然而，MC在先天免疫和适应性免疫、自身免疫、移植排斥、血管疾病、肿瘤生长和伤口愈合等重要领域的功能目前缺乏明确的证据。该领域的一个主要障碍是缺乏一种基因定义的小鼠突变体选择性和完全缺乏所有MC。目前的MC缺陷模型不是选择性MC缺陷，而是依赖于多益生长因子受体Kit的突变，导致免疫系统内外多个谱系的缺陷。我们现在已经产生了一种选择性mc缺陷的新小鼠品系。Cre介导的MC根除（Cre- master）利用了Cre的遗传毒性，并且不依赖于Cre介导的loxp侧基因的缺失。在这个项目中，我们将探讨MC在先天和适应性免疫反应、细菌感染和败血症以及关节炎、脑脊髓炎和哮喘等自身免疫模型中的作用。

In many physiological and pathological conditions, mast cells (MC) are thought to play important roles beyond allergic disease. However, definitive evidence for MC functions in areas as important as innate and adaptive immunity, autoimmunity, transplant rejection, vascular diseases, tumour growth, and wound healing is currently lacking. A major hurdle in this field is the lack of a genetically-defined mouse mutant selectively and fully deficient in all MC. Current MC deficiency models are not selectively MC deficient but rely on mutations in the pleiotropic growth factor receptor Kit causing defects in multiple lineages inside and outside of the immune system. We have now generated a new mouse strain that is selective MC-deficient. Cre-mediated MC eradication (Cre-Master) takes advantage of the genotoxicity of Cre, and is independent of Cre-mediated deletion of loxP-flanked genes. In this project, we will probe the role of MC in innate and adaptive immune responses, in bacterial infections and sepsis, and in models of autoimmunity such as arthritis, encephalomyelitis and asthma.