自身炎症性综合征（Autoinflammatroy syndromes）是包括多病种的一类遗传性疾病，表现为周期性发热、多器官系统性炎症、进行性脂肪缺失等；以固有免疫系统的调节异常为特征，发病机理不明确，没有特异性治疗方法。我实验组获得一确定的昆明（KM）小鼠自发突变，携带稳定遗传表型，皮肤及全身多系统炎症，随月龄增长体内脂肪组织逐渐减少，与上述自身炎症性疾病中"粒细胞性皮肤病合并脂肪营养不良和发热综合征（CANDLE syndrome）"的临床表现非常相似。本课题拟以SNP多态性标记分型的方法定位并克隆其突变基因，研究突变基因的功能，从固有免疫分子通路入手探讨其发病机制，探索是否可作为人自身炎症性疾病的动物模型，用于对自身炎症性疾病的研究。

Autoinflammatory syndromes represent a group of disorders, which are characterized by periodic fever, multi-organ inflammation, and progressive loss of body fat. Many antoinflammatory syndromes are hereditary. It is believed that abnormal immune responses are the underlying cause of autoinflammatory syndromes, leading to uncontrolled inflammation throughout the body, such as in the skin and joints. However, the exact cause of autoinflammatory syndrome is unclear. Besides palliative care, there is no cure for this disorder. We identified a spontaneous mutant line from the Kunming (KM) mouse line widely used in China. Our prior studies demonstrated that this mutant KM mouse line displayed multi-organ inflammation, progressive loss of body fat, and elevated body temperature, resembling autoinflammatory syndrome, especially a subtype, the CANDLE syndrome. In this proposal, we aim to identify the genetic abnormality associated with this mutant KM line, and investigate the molecular mechanism underlying its associated phenotypes. These studies may determine if this mutant KM line can be used as a mouse model of CANDLE syndrome, and contribute to the understanding of the initiation and progression of autoinflammatory syndromes.