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Keywords:

  • costamere;
  • dystroglycan;
  • dystrophin;
  • Largemyd;
  • muscular dystrophy;
  • myd;
  • myodystrophy;
  • sarcoglycan;
  • sarcolemma;
  • spectrin;
  • syntrophin

Abstract

In the Largemyd 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 Largemyd 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 Largemyd mice contain reduced levels of several membrane cytoskeletal proteins, including dystrophin and β-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 Largemyd muscles. We propose that the absence of the dystrophin complex from these regions destabilizes the sarcolemma of the Largemyd 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. Muscle Nerve, 2004