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-1ra)是一种自然产生的多肽 这与IL-1β有26%的同源性。通过占用白介素1(IL-1) 1)受体位置，但不能启动细胞对IL-1的反应， IL-1ra可能是IL-1介导的炎症过程的抑制因子。 IL-1ra已被证明在以下情况下抑制炎症反应 将重组蛋白注射到动物体内。为了测试 IL-1ra是否是IL-1相关炎症的内源性调节因子 在体内的过程中，小鼠将被基因操纵为 缺乏IL-1ra基因(‘基因敲除’)，或有多余的 IT(“转基因”)。这将提供一种工具，其中的效果 内源性IL-1ra已经完全消除，或者其中有额外的拷贝 可赋予基因产物的相加效应。淘汰赛和 然后，转基因小鼠将根据胚胎和胎儿的特征进行表征 自发性炎症性疾病的发展及趋势 精神错乱。对炎症的敏感性将通过以下方式测试 炎症的三种实验模型及其特征 转基因和基因敲除小鼠：内毒素休克，单关节 (类风湿性)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.