Genomic structure, functional comparison, and tissue distribution of mouse Cd59a and Cd59b
Genomic structure, functional comparison, and tissue distribution of mouse Cd59a and Cd59b
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DOI：
10.1007/s00335-001-2060-8
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发表时间：
2001-08-01
期刊：
影响因子：
2.5
通讯作者：
Halperin, JA
中科院分区：
文献类型：
--
作者：
Qin, XB;Miwa, T;Halperin, JA
CD 59是一种重要的补体调节蛋白，其通过干扰C9与C5 b-8的结合来抑制补体激活级联的末端步骤，从而防止膜攻击复合物（MAC）的形成。我们最近报道，小鼠基因组含有两个Cd 59基因，而人类和大鼠基因组各含有一个Cd 59基因（Qian et al. 2000）。在这里，我们描述的基因组结构，比较活性，和组织分布这两个小鼠基因，指定Cd 59 a和Cd 59 b。小鼠Cd 59基因包含总共45.6kb，每个基因具有四个外显子，Cd 59 a跨度19 kb，Cd 59 b跨度15 kb，两个基因之间有大约11.6kb的基因组DNA。Cd 59 a和Cd 59 b之间的总体序列相似性约为60%。两个基因的外显子2、外显子3和外显子4及其侧翼序列的相似性均在85%以上，而外显子1及其侧翼序列完全不同。对两个基因作为MAC形成抑制剂的活性的比较研究表明，Cd 59 b的比活性是Cd 59 a的6倍。使用多克隆抗体的Cd 59 a或Cd 59 b，我们发现，Cd 59 a和Cd 59 b都广泛表达在肾脏。脑、肺、脾和睾丸，以及大多数小鼠组织的血管中。有趣的是，睾丸Cd 59 a似乎只在精子细胞中表达，而Cd 59 b在更成熟的精子细胞中表达。这些结果表明，尽管Cd 59 a和Cd 59 b在多种组织中表达，但它们可能发挥一些不同的作用，特别是在生殖中。
CD59 is a crucial complement regulatory protein that inhibits the terminal step of the complement activation cascade by interfering with the binding of C9 to C5b-8, thus preventing the formation of the membrane attack complex (MAC). We recently reported that the mouse genome contains two Cd59 genes, while the human and rat genomes each contain only one Cd59 gene (Qian et al. 2000). Here, we describe the genomic structure, comparative activity, and tissue distribution of these two mouse genes, designated Cd59a and Cd59b. The mouse Cd59 genes encompass a total of 45.6 kb with each gene having four exons, Cd59a spans 19 kb, and Cd59b spans 15 kb, with approximately 11.6 kb of genomic DNA separating the two genes. The overall sequence similarity between Cd59a and Cd59b is approximately 60%. The sequence similarity between exon 2, exon 3, and exon 4 and the respective flanking regions between the two genes is over 85%, but exon 1 and its flanking regions are totally different, Comparative studies of the activity of both genes as inhibitors of MAC formation revealed that Cd59b has a specific activity that is six times higher than that of Cd59a. Using polyclonal antibodies specific to either Cd59a or Cd59b, we showed that Cd59a and Cd59b are both widely expressed in the kidneys. brain, lungs, spleen, and testis, as well as in the blood vessels of most mouse tissues. Interestingly, testicular Cd59a appeared to be expressed exclusively in spermatids, whereas Cd59b was expressed in more mature sperm cells. These results suggest that even though Cd59a and Cd59b are expressed in multiple tissues, they may play some different roles, particularly in reproduction.