Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration.
Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient regeneration of skeletal muscle along with transient expression of dystroglycan in regenerating muscle fibers. We demonstrate a similar phenomenon of reexpression of functional dystroglycan in regenerating muscle fibers in a mild form of human muscular dystrophy caused by disruption of posttranslational dystroglycan processing. Thus, maintenance of regenerative capacity by satellite cells expressing dystroglycan is likely responsible for mild disease progression in mice and possibly humans. Therefore, inadequate repair of skeletal muscle by satellite cells represents an important mechanism affecting the pathogenesis of muscular dystrophy.
Cohn
Ronald D
RD
Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, Iowa City, IA 52242, USA.
Henry
Michael D
MD
Michele
Daniel E
DE
Barresi
Rita
R
Saito
Fumiaki
F
Moore
Steven A
SA
Flanagan
Jason D
JD
Skwarchuk
Mark W
MW
Robbins
Michael E
ME
Mendell
Jerry R
JR
Williamson
Roger A
RA
Campbell
Kevin P
KP
D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D049030:Dystroglycans; D006984:Hypertrophy; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics*; D011995:Recombination, Genetic; D012038:Regeneration
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049030:Dystroglycans