title: Distribution of ten laminin chains in dystrophic and regenerating muscles.
abstract: Using immunohistochemical methods, we assessed the distribution of all 10 known laminin chains (alpha1-5, beta1-3, gamma1 and gamma2) in skeletal muscles from patients with Duchenne, congenital, limb girdle, or Emery-Dreifuss muscular dystrophies. The alpha2, beta1 and gamma1 chains were abundant in the basal lamina surrounding muscle fibers in normal controls; alpha1, alpha3-alpha5, beta3, and gamma2 were undetectable; and beta2 was present at a low level. Compared to controls, levels of the alpha5 chain were increased in muscles from many dystrophic patients; levels of beta1 were reduced and/or levels of beta2 were increased in a minority. However, these changes were neither specific for, nor consistent within, diagnostic categories. In contrast, levels of alpha4 were increased in muscles from all patients with alpha2 laminin (merosin)-deficient congenital muscular dystrophy. Loss of alpha2 laminin in congenital dystrophy is disease-specific but some other changes in laminin isoform expression in dystrophic muscles could be secondary consequences of myopathy, denervation, regeneration or immaturity. To distinguish among these possibilities, we compared the laminins of embryonic, denervated, regenerating, and mutant mouse muscles with those in normal adult muscle. Embryonic muscle basal lamina contained alpha4 and alpha5 along with alpha2, and regenerating muscle re-expressed alpha5 but not alpha4. Levels of alpha5 but not alpha4 were increased in dystrophin (mdx) mutants and in dystrophin/utrophin double mutants (mdx:utrn -/-), models for Duchenne dystrophy. In contrast, laminin alpha4 was upregulated more than alpha5 in muscles of laminin alpha2 mutant mice (dy/dy; a model for alpha2-deficient congenital dystrophy). Based on these results, we hypothesize that the expression of alpha5 in many dystrophies reflects the regenerative process, whereas the selective expression of alpha4 in alpha2-deficient muscle is a specific compensatory response to loss of alpha2.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical Center, St. Louis, MO, 63110, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Patton
authors.forename: A M
authors.initials: AM
authors.lastname: Connoll
authors.forename: P T
authors.initials: PT
authors.lastname: Martin
authors.forename: J M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: J H
authors.initials: JH
authors.lastname: Miner
authors.forename: J R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000473:pathology; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology* / Q000502:physiology*; D009136:Muscular Dystrophies / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000473:pathology; D012038:Regeneration
chemical_list: D007797:Laminin