Genetic analysis of the interaction between cardiac and skeletal actin gene expression in striated muscle of the mouse

Abstract

The two sarcomeric actin genes, encoding α-cardiac and α-skeletal actins, are co-expressed in striated muscle, but in the adult the respective isoform predominates in cardiac or skeletal muscle of the normal mouse. We have investigated the interaction between this gene pair in different genetic contexts. Northern blot analysis of α-actin mRNA levels in different inbred mice (129/SJ, C3H, C57BL/6) demonstrates variation of as much as threefold in skeletal muscle and eightfold in cardiac muscle. High or low-level expression is seen for both skeletal and cardiac muscle in a given line, suggesting common regulatory phenomena affecting the abundant α-skeletal or α-cardiac transcript. In the BALB/c mouse, which has a mutant cardiac actin locus, skeletal as well as cardiac actin mRNA and protein accumulate in the adult heart. We have analysed the role of the two α-actin genes in this phenomenon in seven recombinant inbred mouse lines (BALB/c × C57BL/6) and in a cross (BALB/c × C3H). The results demonstrate that neither α-actin gene alone is sufficient, and implicate other regulatory loci. DNA sequencing of the C3H and BALB/c α-skeletal actin gene promoters shows that they are virtually identical over 830 nucleotides. The relative levels of α-skeletal and α-cardiac actin proteins have been measured by N-terminal peptide analysis in the different mouse lines. The results point to regulatory loci affecting mRNA utilization and protein stability.