cDNA clone spanning the alpha-gamma subunit junction in the precursor of the murine fourth complement component (C4)

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• The fourth complement component (C4) is a crucial protein in the immune system's complement cascade.
• Genetic variations between mouse strains can lead to significant differences in C4 production and plasma levels.
• Understanding the molecular basis of these differences is essential for studying immune responses and complement function.

Purpose of the Study:

• To identify and characterize cDNA clones encoding murine C4 mRNA sequences.
• To investigate the molecular basis for strain-specific differences in C4 production.
• To correlate differences in C4 protein levels with C4 mRNA expression in the liver.

Main Methods:

• Differential hybridization of mRNA from high (B10.WR) and low (B10.BR) C4-producing mouse strains.
• Hybrid-selected translation to identify functional C4 mRNA sequences.
• DNA sequence analysis of identified cDNA clones, including pMLC4/w7-2.

Main Results:

• Identification of a cDNA clone, pMLC4/w7-2, containing an open reading frame with homology to human C4 gamma-chain.
• Predicted amino acid sequence upstream of tandem arginines shows similarity to the human C4 alpha-chain COOH terminus, suggesting complex post-translational processing.
• Strain differences in plasma C4 levels are directly reflected in the steady-state levels of liver C4 mRNA.

Conclusions:

• The study provides molecular insights into the genetic regulation of murine C4 production.
• Findings suggest that differences in C4 mRNA levels are the primary determinant of C4 protein variation between mouse strains.
• The results raise questions about the post-translational processing of the C4 alpha-chain.