Expression of dystrophin-associated proteins in dystrophin-positive muscle fibers (revertants) in Duchenne muscular dystrophy.
The dystrophin-glycoprotein complex spans the sarcolemma to provide a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix in skeletal muscle. In Duchenne muscular dystrophy (DMD), the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins in the sarcolemma, thus causing the disruption of the dystrophin-glycoprotein complex and the loss of the linkage to the extracellular matrix. This is presumed to lead to sarcolemmal instability which could render muscle fibers susceptible to necrosis. In DMD, a very small percentage of muscle fibers show dystrophin staining along the sarcolemma, presumably due to a second in-frame deletion in the dystrophin gene. However, the functional significance of these rare dystrophin-positive muscle fibers (revertants) in DMD has been unclear. Here we report the co-expression of the dystrophin-associated proteins with dystrophin in revertants of DMD skeletal muscle. Our results suggest that the entire dystrophin-glycoprotein complex is restored in revertants and, thus, the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix is restored in these muscle fibers.
Matsumura
K
K
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Tomé
F M
FM
Collin
H
H
Leturcq
F
F
Jeanpierre
M
M
Kaplan
J C
JC
Fardeau
M
M
Campbell
K P
KP
D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism*; D013194:Staining and Labeling
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049030:Dystroglycans