Distribution of ten laminin chains in dystrophic and regenerating muscles

Using immunohistochemical methods, we assessed the distribution of all 10 known laminin chains (alpha 1-5, beta 1-3, gamma 1 and gamma 2) in skeletal muscles from patients with Duchenne, congenital, limb girdle, or Emery-Dreifuss muscular dystrophies. The alpha 2, beta 1 and gamma 1 chains were abundant in the basal lamina surrounding muscle fibers in normal controls; alpha 1, alpha 3-alpha 5, beta 3, and gamma 2 were undetectable; and beta 2 was present at a low level. Compared to controls, levels of the alpha 5 chain were increased in muscles from many dystrophic patients; levels of beta 1 were reduced and/or levels of beta 2 were increased in a minority. However, these changes were neither specific for, nor consistent within, diagnostic categories. In contrast, levels of alpha 4 were increased in muscles from all patients with alpha 2 laminin (merosin)-deficient congenital muscular dystrophy. Loss of alpha 2 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 alpha 4 and alpha 5 along with alpha 2, and regenerating muscle re-expressed alpha 5 but not alpha 4. Levels of alpha 5 but not alpha 4 were increased in dystrophin (mdx) mutants and in dystrophin/utrophin double mutants (mdx:utrn -/-), models for Duchenne dystrophy. In contrast, laminin alpha 4 was upregulated more than alpha 5 in muscles of laminin alpha 2 mutant mice (dy/dy; a model for alpha 2-deficient congenital dystrophy). Based on these results, we hypothesize that the expression of alpha 5 in many dystrophies reflects the regenerative process, whereas the selective expression of alpha 4 in alpha 2-deficient muscle is a specific compensatory response to loss of alpha 2. (C) 1999 Elsevier Science B.V. All rights reserved.