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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.

该计划的总体目标是定义 C 的角色宿主防御机制中的反应蛋白（CRP）。它一直假设，主要基于体外研究，CRP 功能在炎症刺激后的早期免疫前阶段。一个 CRP 在体内炎症反应过程中的明确作用尚未成立。在之前的资助期间，本金研究人员培育出表达兔 CRP 的转基因小鼠金属硫蛋白 (MTT) 或 PEPCK 启动子，这使得 CRP 的表达与炎症刺激无关。这些转基因动物已被用于三种炎症小鼠模型，包括 LPS 和 PAF 的全身效应（肺泡模型）炎症和单关节关节炎模型。在所有三个表达 CRP 的转基因小鼠系统已显示出可重复性抗炎作用。目前的建议是扩大研究范围关于 CRP 作为炎症参与者的机制，假设 CRP 的作用取决于它的能力结合磷酸胆碱 (PC)，CRP 可以影响细胞因子的表达粘附分子和对抗原产生的抗炎作用关节炎是通过抑制 T 细胞活化介导的免疫过程的传入臂。这些假设将通过以下方式进行检验： 1) 产生表达突变型CRP的转基因小鼠，该突变型CRP已被设计为无法与PC绑定； 2) 测量CRP的效果对单核细胞、脾细胞和炎症细胞因子基因表达的影响中性粒细胞； 3) 在术前、术中和术中控制 CRP 水平在关节炎模型中启动免疫反应后确定 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）

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

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

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