STRUCTURE AND EXPRESSION OF COMPLEMENT GENES

小鼠主要组织相容性复合体（H-2）的S区是 20年前被定义为一个基因位点，控制着 小鼠血清中的Ss（血清物质）蛋白。 从那时起，从一个 许多实验室已经确定，S是由两个不同的 蛋白质：C4，小鼠补体的第四组分，和Slp（用于 性别限制蛋白），一种与人类具有广泛结构和 与C4具有生物化学同源性，但缺乏补体活性。 Slp是 不同之处在于，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丸激素水平，而对于其他菌株， 它的合成要么不依赖于睾酮水平，要么 不可检测 遗传学分析表明，S区含有 C4和Slp的不同结构基因。 该计划的目标是利用核酸克隆技术， 测序方法（1）建立C4和Slp的结构 分子，（2）以确定其各自的相对位置 H-2复合物中的基因，以及（3）检查核酸的性质 结构变异赋予改变的蛋白质功能水平， 活性和蛋白表达。 我们积累的结构信息 应该提供深入了解补体的进化和鼠 组织相容性复合物，C4和Slp表达的调节，以及 C4、Slp和两种密切相关的蛋白质之间的结构/功能关系 补体成分，C3和C5。

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.