REGULATION OF C REACTIVE PROTEIN GENE EXPRESSION

这份申请书是为了继续支持我们对 急性时相五肽C反应的分子调控 蛋白(CRP)及其同源血清淀粉样蛋白P组分(SAP) 相关的急性时相蛋白、血清淀粉样蛋白A(SAA)。这个 研究过程中产生的cDNAs和基因组克隆的可用性 最初的资助期提供了实施建议的试剂 喷淋新等急性期基因作用机制的研究 细胞的调控及其与病理生理学的关系 淀粉样变性。具体地说，我们计划：1)完成 人五肽基因的特性及其比较 相应的仓鼠基因。2)确定 五肽和SAA基因表达调控机制的研究 确定调解人以及 这些基因两侧的启动子和增强子序列。3) 检查肝脏和肝外表达的基础 萨阿。为了实现这些目标，我们将使用噬菌体和粘粒 克隆方法，瞬时和稳定的转基因系统，在 体外转录和翻译分析及原位分析 杂交技术。一款优秀模型的可用性 叙利亚仓鼠淀粉样变性的基因序列及各基因的克隆 相关的蛋白质可以将这些基因与 相应的人类基因和基因产物。一个基础 急性心肌梗死致淀粉样变性过程的认识 应产生位相刺激。拟议的研究将包括 理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 通过媒介控制炎症。

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.