CARDIAC AND SKELETAL MYOPATHY IN BETA-MYOSIN HEAVY-CHAIN SIMIAN-VIRUS-40 TSA58-TRANSGENIC MICE

The mechanisms regulating cardiac muscle differentiation and developme nt are incompletely understood. To examine the relationships between c ardiocyte proliferation and differentiation, we tested the ability of a fragment from the rat beta myosin heavy-chain (MHC beta) gene to cor rectly target expression of a thermolabile simian virus 40 large tumor antigen allele (tsA58) in the developing mouse. Transgene expression in the heart was observed as early as 10 days postconception and was d evelopmentally regulated in parallel with the endogenous MHC beta gene . Expression was also detected in developing skeletal muscle, although at low levels. Despite the temperature sensitivity of the mutant larg e tumor antigen protein, a subset of transgenic mice in several lineag es developed marked cardiac and skeletal myopathies.