Trans-regulatory genes affect Slpa and Slpo expression and act in a tissue-specific manner.

The plasma protein C4 and its androgen-dependent homologue Slp are encoded by genes located in the mouse major histocompatibility complex, H-2. The C4 and Slp protein levels and liver mRNA levels are influenced by non-H-2-linked regulatory genes. The allele-specific regulation of C4 expression and the androgen regulation of Slp expression are manifest only in some of the tissues where these genes are expressed. Therefore, we studied tissues in which the effects of the non-H-2 regulatory genes are apparent. We show that these genes only affect the Slp expression in tissues where it is androgen-dependent. This indicates that the non-H-2 regulatory genes most likely act through interaction with the androgen regulation of Slp expression. We also show that liver cells of mice with the Slpo allele, which do not produce Slp protein, do express Slp mRNA; this expression is also androgen-induced and regulated by non-H-2 genes. Thus, both the Slpa and Slpo alleles appear to be regulated in the same way.