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：
6055588
负责人：
DAVID SAMOLS
金额：
$ 19.61万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
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 2001-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6055588
关键词：
acute phase protein arthritis cell adhesion molecules chemical binding cytokine gene expression genetically modified animals immunity inflammation laboratory mouse leukocyte activation /transformation molecular site phosphoenolpyruvate carboxylase phosphorylcholine protein structure function tissue /cell culture

项目摘要

The overall objective of this program is to define the role of C reactive protein (CRP) in host defense mechanisms. It has been hypothesized, based largely on in vitro studies, that CRP functions during the early preimmune stages following inflammatory stimulus. A clear role for CRP during the course of inflammatory response in vivo has not been established. In the prior funding period the principal investigator has generated transgenic mice which express rabbit CRP with either a metallothionein (MTT) or PEPCK promoter which has made possible expression of CRP independent of inflammatory stimuli. These transgenic animals have been used in three mouse models of inflammation which include the systemic effects of LPS and PAF, a model of alveolar inflammation and a model of monoarticular arthritis. In all three systems CRP expressing transgenic mice have shown reproducible antiinflammatory effects. The present proposal is to extend the studies on the mechanisms of CRP as a participant in inflammation, The working hypotheses are that the effects of CRP are dependent on its ability to bind phosphocholine (PC), CRP can influence expression of cytokines and adhesion molecules, and antiinflammatory effects on antigen enduced arthritis are mediated by inhibition of T cell activation during the afferent arm of the immune process. These hypotheses will be tested by: 1) producing transgenic mice expressing a mutant CRP which has been designed to be incapable of PC binding; 2) measuring the effects of CRP on inflammatory cytokine gene expression in monocytes, splenocytes and neutrophils; and 3) manipulating the level of CRP before, during and after the initiation of the immune response in a model of arthritis to determine the effect of CRP on T cell activation.

该计划的总体目的是定义C的作用宿主防御机制中的反应性蛋白质（CRP）。它一直假设基于体外研究，CRP功能在炎症刺激后的免疫前阶段。一个在体内炎症反应过程中，CRP的角色明确尚未建立。在以前的资助期内研究者已经产生了转基因小鼠，该小鼠用金属胸蛋白（MTT）或PEPCK启动子已成为可能 CRP的表达与炎症刺激无关。这些转基因动物已用于三种炎症的小鼠模型中包括LPS和PAF的系统效应，牙槽模型炎症和单关节炎的模型。在这三个表达转基因小鼠的系统CRP已显示可再现抗炎作用。目前的提议是扩展研究关于CRP作为炎症参与者的机制，工作假设是CRP的影响取决于其的能力结合磷胆碱（PC），CRP可以影响细胞因子的表达和粘附分子和对抗原的抗炎作用关节炎是通过抑制T细胞激活的介导的免疫过程的传入臂。这些假设将通过： 1）产生表达突变体CRP的转基因小鼠设计为无PC结合； 2）测量CRP的影响在单核细胞，脾细胞和中性粒细胞； 3）操纵CRP之前，之中和在关节炎模型中开始免疫反应后确定CRP对T细胞激活的影响。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Transgenic mice expressing C-reactive protein are susceptible to infection with Plasmodium yoelii sporozoites.

表达 C 反应蛋白的转基因小鼠容易受到约氏疟原虫子孢子的感染。

DOI：
10.1128/iai.61.1.348-349.1993
发表时间：
1993
期刊：
Infection and immunity
影响因子：
3.1
作者：
Rénia,L;Xia,D;Samols,D;Nussenzweig,V
通讯作者：
Nussenzweig,V

Intrasplenic immunization with infected hepatocytes: a mouse model for studying protective immunity against malaria pre-erythrocytic stage.

用受感染的肝细胞进行脾内免疫：用于研究红细胞前期疟疾保护性免疫的小鼠模型。

DOI：
发表时间：
1994
期刊：
Immunology
影响因子：
6.4
作者：
Rénia,L;Rodrigues,MM;Nussenzweig,V
通讯作者：
Nussenzweig,V

Generation of deletion mutants by partial digestion.

通过部分消化产生缺失突变体。

DOI：
发表时间：
1995
期刊：
BioTechniques.
影响因子：
0
作者：
Zhang,D;Xia,D;Samols,D
通讯作者：
Samols,D

Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia.

DOI：
10.1073/pnas.94.6.2575
发表时间：
1997-03
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
D. Xia;D. Samols
通讯作者：
D. Xia;D. Samols