Aberrant expression of myosin isoforms in skeletal muscles from mice lacking the rev-erbAα orphan receptor gene

The rev-erbAα orphan protein belongs to the steroid nuclear receptor superfamily. No ligand has been identified for this protein, and little is known of its function in development or physiology. In this study, we focus on 1) the distribution of the rev-erbAα protein in adult fast- and slow-twitch skeletal muscles and muscle fibers and 2) how the rev-erbAα protein influences myosin heavy chain (MyHC) isoform expression in mice heterozygous (+/−) and homozygous (−/−) for a rev-erbAα protein null allele. In the fast-twitch extensor digitorum longus muscle, rev-erbAα protein expression was linked to muscle fiber type; however, MyHC isoform expression did not differ between wild-type, +/−, or −/− mice. In the slow-twitch soleus muscle, the link between rev-erbAα protein and MyHC isoform expression was more complex than in the extensor digitorum longus. Here, a significantly higher relative amount of the β/slow (type I) MyHC isoform was observed in both rev-erbAα −/− and +/− mice vs. that shown in wild-type controls. A role for the ratio of thyroid hormone receptor proteins α1 to α2 in modulating MyHC isoform expression can be ruled out because no differences were seen in MyHC isoform expression between thyroid hormone receptor α2-deficient mice (heterozygous and homozygous) and wild-type mice. Therefore, our data are compatible with the rev-erbAα protein playing an important role in the regulation of skeletal muscle MyHC isoform expression.