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

基因定义和选择性肥大细胞缺陷小鼠模型揭示肥大细胞的免疫作用

• 批准号: 125336747
• 负责人: Professor Dr. Hans-Reimer Rodewald
• 金额: --
• 依托单位: Deutsches Krebsforschungszentrum (DKFZ)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/125336747?language=en
• 关键词: Genetically; defined; selectively; mast; cell

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.

在许多生理和病理条件下，肥大细胞(MC)被认为在变态反应性疾病之外发挥着重要作用。然而，MC在先天和获得性免疫、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发挥作用的确凿证据目前尚不清楚。这一领域的一个主要障碍是缺乏一种在所有MC中选择性和完全缺陷的遗传定义的小鼠突变。目前的MC缺乏模型并不是选择性的MC缺陷，而是依赖于多效性生长因子受体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新的小鼠品系，它是选择性MC缺陷的。Cre介导的MC根除(Cre-Master)利用了Cre的遗传毒性，不依赖于Cre介导的loxP基因缺失。在这个项目中，我们将探讨MC在先天性和获得性免疫反应、细菌感染和败血症以及自身免疫模型(如关节炎、脑脊髓炎和哮喘)中的作用。