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GENETICALLY MODIFIED ANIMALS AND MODEL ORGANISMS

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

¹Center for Development and Health Genetics, Pennsylvania State University, University Park, Pennsylvania; ²Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; and ³Department of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, Sweden

Submitted 2 December 2003 ; accepted in final form 13 September 2004

The rev-erbA 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-erbA protein in adult fast- and slow-twitch skeletal muscles and muscle fibers and 2) how the rev-erbA protein influences myosin heavy chain (MyHC) isoform expression in mice heterozygous (+/–) and homozygous (–/–) for a rev-erbA protein null allele. In the fast-twitch extensor digitorum longus muscle, rev-erbA 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-erbA protein and MyHC isoform expression was more complex than in the extensor digitorum longus. Here, a significantly higher relative amount of the /slow (type I) MyHC isoform was observed in both rev-erbA –/– and +/– mice vs. that shown in wild-type controls. A role for the ratio of thyroid hormone receptor proteins ₁ to ₂ in modulating MyHC isoform expression can be ruled out because no differences were seen in MyHC isoform expression between thyroid hormone receptor ₂-deficient mice (heterozygous and homozygous) and wild-type mice. Therefore, our data are compatible with the rev-erbA protein playing an important role in the regulation of skeletal muscle MyHC isoform expression.

orphan nuclear receptors; thyroid hormone; fast- and slow-twitch muscle

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				S. N. Ramakrishnan, P. Lau, L. J. Burke, and G. E. O. Muscat Rev-erb{beta} Regulates the Expression of Genes Involved in Lipid Absorption in Skeletal Muscle Cells: EVIDENCE FOR CROSS-TALK BETWEEN ORPHAN NUCLEAR RECEPTORS AND MYOKINES J. Biol. Chem., March 11, 2005; 280(10): 8651 - 8659. [Abstract] [Full Text] [PDF]