Molecular cloning of the C6A form cDNA of the mouse sixth complement component: functional integrity despite the absence of factor I modules

Abstract.

The sixth complement component (C6) is an essential component of the biologically active C5b-9 membrane attack complex of the complement system. The multimolecular C5b-9 complex is an important mediator of the biological effects of the activated complement system through its prominent cell signaling and cytolytic functions. To begin to provide essential information and reagents needed to analyze the functions of the complement system in mouse models of human diseases, the cDNA of the A form of mouse C6, which is present in all mouse strains, was cloned and characterized structurally and functionally. Although strikingly homologous in deduced amino acid sequence and modular structure to human C6 (75% identity), mouse C6 is substantially smaller due to the absence of the two carboxyl-terminal factor I modules (FIMs) found in human C6. Various approaches, including studies with antibody generated to recombinant mouse C6, failed to reveal evidence for FIMs in this form of mouse C6. Despite the absence of these modules in C6A, reported to be important for interactions with C5 in the human system, mouse C6A is functionally active and is readily incorporated into the mouse C5b-9 complex.