THE MEMBRANE-CYTOSKELETON INTERFACE - THE ROLE OF DYSTROPHIN AND UTROPHIN

Recent studies with transgenic animals have considerably advanced our knowledge of the roles of dystrophin and utrophin in both muscle and n on-muscle tissues. Rigorous analyses of the roles of the various mdx m utations in mice, as well as the use of artificial transgenes in an md x background, are beginning to define the functional importance of var ious regions of the dystrophin protein in normal muscle. Furthermore, recent biochemical analyses have revealed new insights into the role a nd organization of dystrophin at the membrane-cytoskeleton interface. Transgenic approaches have also revealed surprising and encouraging re sults with respect to utrophin. Against expectations, the long-awaited utrophin knockout mice have a remarkably mild phenotype with only sub tle changes in neuromuscular junction architecture. On the other hand, mdx mice transgenic for a mini-utrophin construct showed rescue of th e muscular dystrophy phenotype, clearly an encouraging finding with ob vious therapeutic possibilities. These and other recent findings are d iscussed in the context of the structure and function of dystrophin an d utrophin at the membrane-cytoskeleton interface.