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Molecular cloning of the C6A form cDNA of the mouse sixth complement component: functional integrity despite the
J X Yu1, B M Bradt, N R Cooper
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Insights
Researchers cloned and characterized mouse C6, a key part of the complement system. Despite lacking certain human modules, mouse C6A is functional and forms the C5b-9 complex.
Area of Science:
- Immunology
- Molecular Biology
Background:
- The sixth complement component (C6) is crucial for the C5b-9 membrane attack complex.
- The C5b-9 complex mediates complement system's cell signaling and cytolytic functions.
Purpose of the Study:
- To clone and characterize mouse C6 (C6A) for studying complement in mouse disease models.
- To compare mouse C6 structure and function with human C6.
Main Methods:
- Cloning and structural characterization of mouse C6A cDNA.
- Functional analysis of mouse C6A.
- Antibody generation against recombinant mouse C6 for FIMs detection.
Main Results:
- Mouse C6A cDNA was cloned and characterized.
- Mouse C6A shares high homology with human C6 but is smaller due to absent factor I modules (FIMs).
- No evidence for FIMs in mouse C6A was found, yet it is functionally active and forms the C5b-9 complex.
Conclusions:
- Mouse C6A is functionally active and incorporates into the C5b-9 complex, despite lacking FIMs.
- This characterization provides essential reagents and information for complement system research in mouse models.
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.