INTERLEUKIN-1 RECEPTOR ANTAGONIST IN MICE

该研究项目将确定白细胞介素-1在体内的作用 受体拮抗剂（IL-1 ra），其为天然存在的多肽 与IL-1 β有26%的同源性。 通过占据白细胞介素-1（IL- 1)受体位点，但不能启动对IL-1的细胞应答， IL-1 ra可作为IL-1介导的炎症过程的抑制剂。 IL-1 ra已被证明在以下情况下抑制炎症反应： 向动物施用重组蛋白。 为了测试 IL-1 ra是否是IL-1相关炎症的内源性调节剂 在体内过程中，小鼠将被遗传操纵， 缺乏IL-1 ra基因（“敲除”），或具有 转基因（transgenics） 这将提供一种工具， 内源性IL-1 ra已完全消除，或其中额外拷贝 可以赋予基因产物的累加效应。 敲除和 然后，将根据胚胎和胎儿特征来表征转基因小鼠 发展和趋势，自发发生的炎症 紊乱 对炎症的敏感性将通过创建 三种实验性炎症模型， 转基因和基因敲除小鼠：内毒素诱导的休克，单关节 （类风湿）关节炎和子宫内膜异位症。

The research project will determine the in vivo role of interleukin-1 receptor antagonist (IL-1ra) which is a naturally-occurring polypeptide that bears 26% homology to IL-1Beta. By occupying the Interleukin-1 (IL- 1) receptor site, but failing to initiate the cellular response to IL-1, IL-1ra may serve as an inhibitor of IL-1-mediated inflammatory processes. Il-1ra has been shown to inhibit inflammatory responses when the recombinant protein was administered to animals. In order to test whether IL-1ra is an endogenous modulator of IL-1-related inflammatory processes in vivo, mice will be genetically manipulated either to be lacking the IL-1ra gene ('knockouts"), or having supernumerary copies of it ("transgenics"). This will provide a tool in which the effect of endogenous IL-1ra have been totally eliminated, or in which extra copies may confer an additive effect of the gene product. Knockout and transgenic mice will then be characterized in term of embryonic and fetal development and tendency to the spontaneous occurrence of inflammatory disorders. Susceptibility to inflammation will be tested by creating three experimental models of inflammation and characterizing them in transgenic and knockout mice: endotoxin-induced shock, monoarticular (rheumatoid) arthritis and endometriosis.