STRUCTURE AND EXPRESSION OF COMPLEMENT GENES

补体基因的结构和表达

• 批准号: 3277505
• 负责人: Ronald T Ogata
• 金额: $ 11.57万
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-04-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3277505
• 关键词: RNA directed DNA polymerase; chromatography; clone cells; complement; density gradient ultracentrifugation; gel electrophoresis; gene expression; genetic manipulation; histocompatibility gene; hormone regulation /control mechanism; nucleic acid sequence; testosterone

The S region of the murine major histocompatibility complex (H-2) was defined twenty years ago as a genetic locus controlling the quantity of the Ss (serum substance) protein in mouse serum. Since then, work from a number of laboratories has established that Ss is composed of two distinct proteins: C4, the murine fourth component of complement, and Slp (for sex-limited protein), a protein which shares extensive structural and biochemical homology with C4 but which lacks complement activity. Slp is distinctive in that, for some inbred mouse strains, its expression depends entirely or almost entirely on testosterone levels, while for other strains its synthesis is either independent of testosterone levels, or undetectable. Genetic analysis indicates that the S region harbors distinct structural genes for C4 and Slp. The goal of the proposed program is to use nuclei acid cloning and sequencing methods (1) to establish the structures of the C4 and Slp molecules, (2) to determine the relative locations of their respective genes in the H-2 complex, and (3) to examine the nature of nucleic acid structural variations which impart altered levels of protein functional activity and protein expression. The structural information we accumulate should provide insights into the evolution of complement and of the murine histocompatibility complex, the regulation of C4 and Slp expression, and the structure/function relationships among C4, Slp, and two closely related complement components, C3 and C5.

鼠主要组织相容性复合体 (H-2) 的 S 区是 二十年前被定义为控制基因数量的基因位点 小鼠血清中的 Ss（血清物质）蛋白。 从那时起，工作从 许多实验室已确定 Ss 由两个不同的部分组成 蛋白质：C4，小鼠补体的第四种成分，以及 Slp（用于 性别限制蛋白），一种具有广泛结构和 与 C4 生化同源，但缺乏补体活性。 斯利普是 其独特之处在于，对于某些近交系小鼠品系，其表达取决于 完全或几乎完全取决于睾酮水平，而对于其他菌株 它的合成要么独立于睾酮水平，要么 无法检测到。 遗传分析表明S区具有 C4 和 Slp 的不同结构基因。 拟议计划的目标是利用核酸克隆和 测序方法（1）建立C4和Slp的结构 分子，（2）确定它们各自的相对位置 H-2 复合物中的基因，以及 (3) 检查核酸的性质 结构变异导致蛋白质功能水平改变 活性和蛋白质表达。 我们积累的结构信息 应该提供对补体和小鼠的进化的见解 组织相容性复合物、C4 和 Slp 表达的调节，以及 C4、Slp 和两个密切相关的结构/功能之间的关系 补体成分 C3 和 C5。