Regulation of expression of mouse C4 and Slp genes by non-H-2-linked genes

C4 (the fourth complement component) and Slp (sexlimited protein) are two homologous plasma proteins encoded by genes in the S-region of the H-2 gene complex. We studied the genetic factors influencing the plasma levels of these proteins and their mRNA levels in liver. Considerable differences in both protein and mRNA levels were found between mouse strains carrying the same S-region allele on different genetic backgrounds, indicating a pretranslational effect of non-H-2-linked genes on the expression of the two S-region genes. The expression of Slp is androgen-dependent in the strains tested. However, testosterone treatment cannot increase the low levels of Slp caused by non-H-2-linked regulatory genes. In mice with Slp-negative S-region alleles we found liver mRNA hybridizing with Slp-specific oligonucleotides, indicating expression of the Slp gene in Slp-negative strains. Our data demonstrate the complexity of the regulation of the C4 and Slp genes and pave the way for the analysis of the regulatory factors involved.