IN VIVO ROLE OF CRP IN TRANSGENIC MICE
CRP 在转基因小鼠体内的作用
基本信息
- 批准号:3161225
- 负责人:
- 金额:$ 16.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 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
项目摘要
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
项目成果
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DAVID SAMOLS其他文献
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{{ truncateString('DAVID SAMOLS', 18)}}的其他基金
SUBUNITS AND QUATERNARY STRUCTURE OF TRANSCARBOXYLASE
转羧酶的亚基和四级结构
- 批准号:
3298714 - 财政年份:1988
- 资助金额:
$ 16.76万 - 项目类别:
SUBUNITS AND QUATERNARY STRUCTURE OF TRANSCARBOXYLASE
转羧酶的亚基和四级结构
- 批准号:
3298713 - 财政年份:1988
- 资助金额:
$ 16.76万 - 项目类别:
SEQUENCE AND FUNCTIONAL ANALYSIS OF TRANSCARBOXYLASE
转羧酶的序列和功能分析
- 批准号:
3280630 - 财政年份:1985
- 资助金额:
$ 16.76万 - 项目类别:














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