Using immunohistochemical methods, we assessed the distribution of all 10 known laminin chains (α1-5, β1-3, γ1 and γ2) in skeletal muscles from patients with Duchenne, congenital, limb girdle, or Emery-Dreifuss muscular dystrophies. The α2, β1 and γ1 chains were abundant in the basal lamina surrounding muscle fibers in normal controls; α1, α3-α5, β3, and γ2 were undetectable; and β2 was present at a low level. Compared to controls, levels of the α5 chain were increased in muscles from many dystrophic patients; levels of β1 were reduced and/or levels of β2 were increased in a minority. However, these changes were neither specific for, nor consistent within, diagnostic categories. In contrast, levels of α4 were increased in muscles from all patients with α2 laminin (merosin)-deficient congenital muscular dystrophy. Loss of α2 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 α4 and α5 along with α2, and regenerating muscle re-expressed α5 but not α4. Levels of α5 but not α4 were increased in dystrophin (mdx) mutants and in dystrophin/utrophin double mutants (mdx:utrn-/-), models for Duchenne dystrophy. In contrast, laminin α4 was upregulated more than α5 in muscles of laminin α2 mutant mice (dy/dy; a model for α2-deficient congenital dystrophy). Based on these results, we hypothesize that the expression of α5 in many dystrophies reflects the regenerative process, whereas the selective expression of α4 in α2-deficient muscle is a specific compensatory response to loss of α2. Copyright (C) 1999 Elsevier Science B.V.
- Laminin chains, distribution, dystrophic muscle
- Regenerating muscle