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

点击翻译按钮获取中文摘要

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.