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Deficiency of the fifth component of complement in mice with an inherited complement defect
Abstract:
The inherited complement deficiency of certain inbred strains of mice was shown to be due to an isolated lack of the fifth component of complement. The protein MuB1 (or hc'), which is present in normal mouse serum but absent from the serum of complement-deficient mice, was shown to be immunochemically related to the fifth component of human complement (C'5). C'5 hemolytic activity was specifically inhibited in human serum by mouse anti-MuB1 and in normal mouse serum by mouse antiserum to human C'5. Highly purified human C'5 reconstituted the hemolytic activity of complement-deficient mouse serum. It was, therefore, concluded that he', or MuB1, constitutes the murine analogue of the fifth component of human complement. The MuB1 concentration in normal mouse serum was found to be subject to a sex-related variation. By quantitative precipitin analysis it was demonstrated that serum from male mice contains twice as much MuB1 as that of female mice. This difference in C'5 concentration was also detected by hemolytic assay. In addition, C'6 and C'7 were also found to be subject to sex-related variations.
Insights
Mice lacking the fifth component of complement (C'5) were identified. The protein MuB1 was found to be the mouse equivalent of human C'5, with its concentration varying by sex.
Area of Science:
- Immunology
- Genetics
Background:
- Inherited complement deficiencies can arise from specific component absences.
- Certain inbred mouse strains exhibit an isolated deficiency in the fifth component of complement (C'5).
Purpose of the Study:
- To identify the murine analogue of the fifth component of human complement (C'5).
- To investigate sex-related variations in complement component concentrations in mice.
Main Methods:
- Immunochemical analysis to compare mouse protein MuB1 with human C'5.
- Hemolytic assays to assess complement activity.
- Quantitative precipitin analysis to measure protein concentrations.
Main Results:
- The protein MuB1, absent in complement-deficient mice, is immunochemically related to human C'5.
- Mouse anti-MuB1 inhibited human C'5 activity, and anti-human C'5 inhibited normal mouse serum activity.
- Purified human C'5 restored hemolytic activity in deficient mouse serum, confirming MuB1 as the murine C'5 analogue.
- Male mice possess twice the concentration of MuB1 compared to female mice.
- Sex-related variations were also observed for C'6 and C'7.
Conclusions:
- MuB1 is identified as the murine analogue of the fifth component of human complement (C'5).
- Complement component concentrations, including C'5, C'6, and C'7, exhibit significant sex-related variations in mice.