Analysis of the promoters and 5'-UTR of mouse Cd59 genes, and of their functional activity in erythrocytes.

The complement regulatory protein CD59 inhibits formation of the membrane attack complex (MAC), the terminal effector of the complement system. There are two mouse Cd59 genes in mice but only one in humans. In the work reported here we (a) mapped the promoter regions of both mCd59a and mCd59b genes, (b) identified two different promoters for each mCd59 gene, (c) defined a previously unrecognized additional exon 1 in each mCd59 gene, (d) identified that each mCd59 gene expresses two different tissue-specific transcripts that differ in their 5'-UTR, and (e) confirmed the presence of mCd59b mRNA in multiple tissues. At the functional level, comparison of the sensitivity of mCd59ab(-/-) and mCd59a(-/-) red blood cells to MAC-mediated lysis revealed that mCd59b protects RBC from MAC-mediated lysis, at least in the setting of mCd59a deficiency. Together these findings indicate that the mCd59 genes may have complex and perhaps different regulatory mechanisms in different tissues.