REGULATION OF C REACTIVE PROTEIN GENE EXPRESSION

此申请是为了继续支持我们的研究， 急性期正五聚蛋白C反应性的分子调控 蛋白（CRP），其同系物血清淀粉样蛋白P组分（SAP） 以及相关的急性期蛋白血清淀粉样蛋白A（SAA）。 的 cDNA和基因组克隆的可用性 最初的赠款期提供了试剂，以追求拟议的 正五聚蛋白等急性期基因作用机制的研究 调节及其与病理生理学的关系 淀粉样变性 具体而言，我们计划：1）完成 人正五聚蛋白基因的特征和比较 对应的仓鼠基因 2)确定 pentraxin和SAA基因表达的机制， 确定调解人以及 启动子和增强子序列侧翼这些基因。 第三章 检查肝和肝外表达的基础 SAA。 为了实现这些目标，我们将使用噬菌体和粘粒 克隆方法，瞬时和稳定转染系统， 体外转录和翻译分析以及原位 杂交技术 优秀模型的可用性 叙利亚仓鼠中淀粉样变性病的cDNA克隆， 相关的蛋白质允许将这些基因与 相应的人类基因和基因产物。 的基础 对急性心肌梗死引起的淀粉样蛋白生成过程的理解 应该产生相位刺激。 拟议的研究将有 了解真核生物机制的一般意义 基因控制以及与细胞因子相关的问题 介导的炎症控制。

This application is for continued support of our studies of the molecular regulation of the acute phase pentraxin C reactive protein (CRP), its homologue serum amyloid P component (SAP) and the related acute phase protein serum amyloid A (SAA). The availability of cDNA and genomic clones generated during the initial grant period provides the reagents to pursue the proposed studies of mechanisms of pentraxin and other acute phase gene regulation and its relationship to the pathophysiology of amyloidosis. Specifically, we plan to: 1) complete characterization of the human pentraxin genes and compare them to the corresponding hamster genes. 2) Determine the mechanisms involved in pentraxin and SAA gene expression by defining the mediators and the structure and organization of promoter and enhancer sequence flanking these genes. 3) Examine the basis for hepatic and extrahepatic expression of SAA. To accomplish these goals we will use phage and cosmid cloning methods, transient and stable transfection systems, in vitro transcription and translation analysis and in situ hybridization techniques. The availability of an excellent model of amyloidosis in the Syrian hamster and cDNA clones for each of the relevant proteins permit comparisons of these genes to the corresponding human genes and gene products. A basis for understanding of the amyloidogenic process resulting from acute phase stimuli should result. The proposed studies will have general implications for understanding mechanisms of eukaryotic gene control as well as questions specifically related to cytokine mediated control of inflammation.