Post-transcriptional regulation of complement C4 in low C4-producing strain of mouse

The expression of the fourth component of complement (C4) of the mouse can differ 20-fold and is determined by C4-high (C4h) or C4-low (C4l) alleles. To investigate the molecular mechanisms underlying the differences in C4 expression, we compared the transcriptional activity of the C4 genes between high and low C4-producer strains of mice (B10 and FM vs B10.BR) using nuclear transcriptional and chloramphenicol acetyltransferase (CAT) assays. We also compared the level of C4-specific RNA in total and nuclear RNA of the liver. The results revealed no significant difference in transcriptional activity between C4h and C4l genes. However, the steady-state levels of C4 mRNA are ten times lower in C4l strains than in C4h strains, suggesting that the major regulation of C4 plasma levels occurs at the post-transcriptional level.