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BHLH Transcription Factor MyoD Affects Myosin Heavy Chain Expression Pattern In A Muscle-specific Fashion

David J. Seward, John C. Haney, Michael A. Rudnicki, Steven J. Swoap

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A strong correlative pattern between MyoD gene expression and myosin heavy chain IIB (MHC IIB) gene expression exists. To test whether this correlative relationship is causative, MHC gene expression in muscles from MyoD(−/−) mice was analyzed. The MHC IIB gene was not detectable in the MyoD(−/−) diaphragm, whereas the MHC IIB protein made up 10.0 ± 1.7% of the MHC protein pool in the wild-type (WT) mouse diaphragm. Furthermore, the MHC IIA protein was not detectable in the MyoD(−/−) biceps brachii, and the MHC IIB protein was overexpressed in the masseter. To examine whether MyoD is required for the upregulation of the MHC IIB gene within slow muscle after disuse, MyoD(−/−) and WT hindlimb musculature was unweighted. MyoD(−/−) exhibited a diminished response in the upregulation of the MHC IIB mRNA within the soleus muscle as a result of the hindlimb unweighting. Collectively, these data suggest that MyoD plays a role in the MHC profile in a muscle-specific fashion.