ADAPTATIONS IN MYOSIN HEAVY-CHAIN EXPRESSION AND CONTRACTILE FUNCTIONIN DYSTROPHIC MOUSE DIAPHRAGM

The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subs arcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alter ations in diaphragm contractile properties and myosin heavy chain (MHC ) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice . In young mdx mice, maximum isometric tension (P(o)) was reduced to 5 0% of control values. An increase in fibers coexpressing types I (slow ) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, P (o) underwent a further reduction to 25% of control, and there was a s lowing of twitch kinetics along with markedly increased diaphragm endu rance. These changes were associated with an approximate sevenfold inc rease in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We concl ude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power o utput and augmented muscle endurance. In the setting of progressive mu scle fiber destruction, these changes may help preserve contractile fu nction and promote greater survival of remaining muscle fibers by decr easing cellular energy requirements.