ANALYSIS OF MICE DEFICIENT IN C3 RECEPTORS OR REUGLATORS

C3 受体或调节剂缺陷小鼠的分析

• 批准号: 3079378
• 负责人: HECTOR D MOLINA
• 金额: $ 7.47万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079378
• 关键词: Arthus phenomenon; CD3 molecule; T lymphocyte; antigen antibody reaction; autoimmune disorder; complement deficiency; complement receptor; enzyme linked immunosorbent assay; genetically modified animals; humoral immunity; immune complex diseases; immunofluorescence technique; immunoglobulin isotypes; laboratory mouse; light microscopy; microinjections; model design /development; molecular cloning; protein structure function; regulatory gene; surface antigens

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.

许多免疫效应归因于第三成分