Muscle-specific and inducible expression of 293-base pair β-myosin heavy chain promoter in transgenic mice

The DNA regulatory element(s) involved in β-myosin heavy chain (β- MHC) induction by the physiological stimulus of mechanical overload have not been identified as yet. To delineate regulatory sequences that are required for mechanical overload induction of the β-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human β-MHC promoter to nucleotides -293 (β293), -201 (β201), and -141 (β141) from the transcription start site (+1). Mechanically overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous β-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene β293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2-to 2.5-fold) muscles by mechanical overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides β293 and +120 may be sufficient to regulate the endogenous β-MHC gene in response to developmental signals and to the physiological signals generated by mechanical overload in fast- and slow-twitch muscles.