IN VIVO ROLE OF CRP IN TRANSGENIC MICE

CRP 在转基因小鼠体内的作用

• 批准号: 3161225
• 负责人: DAVID SAMOLS
• 金额: $ 16.76万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3161225
• 关键词: acute phase protein; allergic arthritis; amyloid proteins; bacterial endocarditis; binding proteins; biological models; chemical binding; complement pathway; enzyme linked immunosorbent assay; gene expression; genetically modified animals; histochemistry /cytochemistry; inflammation; laboratory mouse; molecular site; phosphorylcholine; protein structure function; site directed mutagenesis; tissue /cell culture; transfection

C-reactive protein (CRP) is an acute phase protein of hepatic origin in man whose plasma concentration increases markedly in response to a wide variety of inflammatory stimuli. CRP is a binding protein which, when bound to one of its ligands, has been found capable of activating complement, and affecting the function of phagocytic cells. CRP also contains tuftsin-like peptides and proteolytic fragments of CRP can stimulate inflammatory cells. These properties along with evolutionary conservation of the protein (which is even found in some invertebrates), have been interpreted as indicating that CRP functions to modulate the inflammatory response. The mouse, in contrast to most vertebrates, does not synthesize a significant quantity of CRP in response to inflammatory stimuli. We have taken advantage of this evolutionary oddity and produced transgenic mice capable of expressing rabbit CRP in order to define the functional role of CRP in vivo. These animals will be employed to assess the effects of rabbit CRP in three established mouse models of inflammation. We will: 1) Initially characterize the properties of CRP in our established transgenic mouse lines. 2) Determine the pathophysiologic and morphologic effects of transgenic CRP on endotoxic shock, antigen-induced acute arthritis and Lactobacillus induced carditis in these animals. 3) Test the in vivo importance of the phosphorylcholine (PC) binding domain of CRP since PC is a ubiquitous substrate to which CRP binds avidly. This domain will be altered by site directed mutagenesis of the rabbit CRP gene and, after confirmation that these mutants are unable to bind PC (following expression in transfected cell lines), will be employed to produce additional transgenic mice. The effects of altering the PC binding domain on the functional properties of CRP will be tested in the models outlined in 1) and 2) above.

c反应蛋白（CRP）是人肝脏源性急性期蛋白