MICE DEFICIENT IN C3 RECEPTORS OR REUGLATORS

许多免疫学效应归因于第三种成分， 补体（C3）由细胞膜受体介导或调节， 调节蛋白，包括补体受体1和2（CR 1，CR2）， 膜辅因子蛋白（MCP）和衰变加速因子（DAF）。 我 一直对这些蛋白质的分析感兴趣， 自身免疫状态，并在动物模型的创建来研究这些 分子。 经过临床培训后，我在V博士工作了三年。 Michael Holers的实验室表征了CR 1和CR2的小鼠同源物， CR2，以及MCP和CR 4的小鼠功能对应物Crry/p65， 蛋白 我在这方面积累了丰富的经验， 分子生物学和免疫学的不同技术。 我克隆 几种小鼠CR 1、CR2和Crry转录物，以及小鼠CR 1、CR2和Crry转录物的一部分， CR 1/CR2基因。 此外，我还建立了我们的遗传关系， 与免疫化学表征的蛋白质同源。 我评估 这些蛋白质的功能，并确定Crry/p65作为一个功能 MCP和BMPs的同源物。 我现在提议制造一只缺乏 这些小鼠补体受体和调节蛋白使用基因 瞄准技术 将分析缺陷小鼠的异常 淋巴发育以及补体介导的组织损伤， T依赖性和T非依赖性抗体应答的失调。 我 主管是大卫卓别林医生。 他有遗传学的背景 补体系统和基因工程方面的大量技术专长 面向. 此外，补语是我们的一个主要研究领域， 流变学分部。 最后，华盛顿大学拥有大量 调查人员谁拥有丰富的经验，在许多方面的 免疫反应，提供了一个良好的环境，以追求这种类型的 research.

Many of the immunological effects attributed to the third component of complement (C3) are mediated or regulated by cell membrane receptors and regulatory proteins, including Complement Receptor l and 2 (CRl,CR2), membrane cofactor protein (MCP), and decay-accelerating factor (DAF). I have been interested in the analysis of these proteins in normal and autoimmune states, and in the creation of animal models to study these molecules. After my clinical training, I have spent three years in Dr. V. Michael Holers' laboratory characterizing the mouse homologues of CRl and CR2, and the mouse functional counterpart of MCP and DAF, the Crry/p65 protein. I have acquired extensive experience in this area and also in different techniques of molecular biology and Immunology. I cloned several mouse CRl, CR2 and Crry transcripts, and a portion of the mouse CRI/CR2 gene. In addition, I established the relation of our genetic homologues with the immunochemically characterized proteins. I evaluated the function of these proteins and identified Crry/p65 as a functional homologue of MCP and DAF. I now propose to create A mouse deficient in these mouse complement receptors and regulatory proteins using gene targeting techniques. The deficient mice will be analyzed for abnormal lymphoid development in addition to complement mediated tissue damage and dysregulation of T-dependent and T-independent antibody responses. My supervisor will be Dr. David Chaplin. He has a background in the genetics of the complement system and substantial technical expertise in gene targeting. Furthermore, complement is a main research area within our Rheumatology division. Finally, Washington University has a large number of investigators who have substantial experience in many aspects of the immune response, providing an excellent environment to pursue this type of research.