title: Immunohistochemical analysis of dystrophin-associated proteins in Becker/Duchenne muscular dystrophy with huge in-frame deletions in the NH2-terminal and rod domains of dystrophin.
abstract: The absence of dystrophin causes the drastic reduction of the dystrophin-associated proteins (DAPs) in the sarcolemma and the loss of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix in Duchenne muscular dystrophy (DMD) skeletal muscle. Here, we report a mild reduction of the DAPs in the unique Becker muscular dystrophy patients with huge deletions in the rod domain of dystrophin and a moderate reduction of the DAPs in patients with huge deletions that involve both the NH2-terminal and rod domains of dystrophin. The phenotype of the latter patients was more severe than that of the former. In both cases, however, the reduction in the DAPs was milder than in typical DMD patients or DMD patients lacking the COOH-terminal domains of dystrophin. Our results suggest that (a) the NH2-terminal and rod domains of dystrophin may not be essential for the interaction with the sarcolemmal glycoprotein complex; and (b) defects in the actin binding activity of dystrophin may cause disruption of the anchorage of the dystrophin-glycoprotein complex to the subsarcolemmal cytoskeleton, which may render muscle fibers susceptible to degeneration.
authors.affiliation: Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: K
authors.initials: K
authors.lastname: Matsumura
authors.forename: A H
authors.initials: AH
authors.lastname: Burghes
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: F M
authors.initials: FM
authors.lastname: Tomé
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: F
authors.initials: F
authors.lastname: Cornello
authors.forename: F
authors.initials: F
authors.lastname: Leturcq
authors.forename: M
authors.initials: M
authors.lastname: Jeanpierre
authors.forename: J C
authors.initials: JC
authors.lastname: Kaplan
authors.forename: P
authors.initials: P
authors.lastname: Reinert
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D008957:Models, Genetic; D008970:Molecular Weight; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017384:Sequence Deletion; D049411:Utrophin
chemical_list: D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D049411:Utrophin