MUSCLE-SPECIFIC AND INDUCIBLE EXPRESSION OF 293-BASE PAIR BETA-MYOSINHEAVY-CHAIN PROMOTER IN TRANSGENIC MICE

The DNA regulatory element(s) involved in beta-myosin heavy chain (bet a-MHC) induction by the physiological stimulus of mechanical overload have not been identified as yet. To delineate regulatory sequences tha t are required for mechanical overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containi ng serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcripti on start site (+1). Mechanically overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endoge nous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltrans ferase specific activity) revealed that only transgene beta 293 expres sion 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 adenosinetri phosphatase activity revealed a fiber-type transition of type II to ty pe I in the overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated b y mechanical overload in fast- and slow-twitch muscles.