Allele-specific occurrence of multiple C4 and Slp mRNAs.

The H-2 S region genes C4 (fourth complement component) and Slp (sex-limited protein) are highly homologous. In males with C4high, Slpa alleles, both proteins are expressed in plasma and the two genes are each transcribed in a single species of mRNA which is indistinguishable in length. The Sk region of the H-2k haplotype carries C4low, Slpo alleles, characterized by very low C4 protein levels in plasma and absence of Slp protein in plasma. We show that mice carrying the Sk region express multiple C4 and Slp mRNAs (RNA doublets) in contrast to mice with any other S region. This represents a genetic polymorphism at the level of RNA multiplicity. The RNA doublets do not result from the use of an alternative upstream initiation site of transcription. We hypothesize that their existence is caused by alternative splicing; however, the use of alternative polyadenylation signals cannot be ruled out. The occurrence of multiple RNA species in strains which carry the C4low, Slpo alleles is possibly related to the very low level of C4 protein expression characteristic for these alleles.