The sarcolemma in the Large(myd) mouse

In the Large(myd) mouse, dystroglycan is incompletely glycosylated and thus cannot bind its extracellular ligands, causing a muscular dystrophy that is usually lethal in early adulthood. We show that the Large(myd) mutation alters the composition and organization of the sarcolemma of fast-twitch skeletal muscle fibers in young adult mice. Costameres at the sarcolemma of the tibialis anterior muscle of Large(myd) mice contain reduced levels of several membrane cytoskeletal proteins, including dystrophin and beta-spectrin. In the quadriceps, longitudinally oriented costameric structures tend to become thickened and branched. More strikingly, proteins of the dystrophin complex present between costameres in controls are absent from Large(myd) muscles. We propose that the absence of the dystrophin complex from these regions destabilizes the sarcolemma of the Large(myd) mouse and thereby contributes to the severity of its muscular dystrophy. Thus, the positioning of sarcolemmal proteins may have a profound effect on the health of skeletal muscle.