1. ¹Department of Medicine, Division of Hematology and Oncology, Brigham and Women's Hospital, Boston, MA, USA
2. ²Laboratory for Translational Research, Harvard Medical School, Cambridge, MA, USA

Correspondence: Dr X Qin, Laboratory for Translational Research, Harvard Medical School, One Kendall Square, Building 600, 3rd Floor, Cambridge, MA 02139, USA. E-mail: xuebin_qin@hms.harvard.edu

Received 8 November 2005; Revised 15 February 2006; Accepted 15 February 2006; Published online 16 March 2006.

Abstract

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.