Genomic structure, functional comparison, and tissue distribution of mouseCd59a and Cd59b

CD59 is a crucial complement regulatory protein that inhibits the terminal step of the complement activation cascade by interfering with the binding o f 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 a l. 2000). Here, we describe the genomic structure, comparative activity, an d 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 fo ur 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 similarit y between Cd59a and Cd59b is approximately 60%. The sequence similarity bet ween 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 t imes higher than that of Cd59a. Using polyclonal antibodies specific to eit her Cd59a or Cd59b, we showed that Cd59a and Cd59b are both widely expresse d 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 mor e mature sperm cells. These results suggest that even though Cd59a and Cd59 b are expressed in multiple tissues, they may play some different roles, pa rticularly in reproduction.