Distribution of ten laminin chains in dystrophic and regenerating muscles

Bruce Patton, Anne M. Connolly, Paul T. Martin, Jeanette M. Cunningham, Shobhna Mehta, Alan Pestronk, Jeffrey H. Miner, Joshua R. Sanes

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)423-433
Number of pages11
JournalNeuromuscular Disorders
Volume9
Issue number6-7
DOIs
StatePublished - Oct 1 1999
Externally publishedYes

Fingerprint

Laminin
Muscles
Dystrophin
Basement Membrane
Emery-Dreifuss Muscular Dystrophy
Utrophin
Denervation
Muscular Diseases
Regeneration
Protein Isoforms
Skeletal Muscle
Extremities

Keywords

  • Laminin chains, distribution, dystrophic muscle
  • Regenerating muscle

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Patton, B., Connolly, A. M., Martin, P. T., Cunningham, J. M., Mehta, S., Pestronk, A., ... Sanes, J. R. (1999). Distribution of ten laminin chains in dystrophic and regenerating muscles. Neuromuscular Disorders, 9(6-7), 423-433. https://doi.org/10.1016/S0960-8966(99)00033-4

Distribution of ten laminin chains in dystrophic and regenerating muscles. / Patton, Bruce; Connolly, Anne M.; Martin, Paul T.; Cunningham, Jeanette M.; Mehta, Shobhna; Pestronk, Alan; Miner, Jeffrey H.; Sanes, Joshua R.

In: Neuromuscular Disorders, Vol. 9, No. 6-7, 01.10.1999, p. 423-433.

Research output: Contribution to journalArticle

Patton, B, Connolly, AM, Martin, PT, Cunningham, JM, Mehta, S, Pestronk, A, Miner, JH & Sanes, JR 1999, 'Distribution of ten laminin chains in dystrophic and regenerating muscles', Neuromuscular Disorders, vol. 9, no. 6-7, pp. 423-433. https://doi.org/10.1016/S0960-8966(99)00033-4
Patton B, Connolly AM, Martin PT, Cunningham JM, Mehta S, Pestronk A et al. Distribution of ten laminin chains in dystrophic and regenerating muscles. Neuromuscular Disorders. 1999 Oct 1;9(6-7):423-433. https://doi.org/10.1016/S0960-8966(99)00033-4
Patton, Bruce ; Connolly, Anne M. ; Martin, Paul T. ; Cunningham, Jeanette M. ; Mehta, Shobhna ; Pestronk, Alan ; Miner, Jeffrey H. ; Sanes, Joshua R. / Distribution of ten laminin chains in dystrophic and regenerating muscles. In: Neuromuscular Disorders. 1999 ; Vol. 9, No. 6-7. pp. 423-433.
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