Duchenne-like myopathy in double-mutant mdx mice expressing exaggerated mast cell activity

J Neurol Sci. 1995 Jul;131(1):1-7. doi: 10.1016/0022-510x(95)00089-k.

Abstract

Dystrophin-deficient female mdx mice were bred with male Tsk+/+ pa mice to examine the role played by mast cells in the pathophysiology of dystrophin deficiency. Resultant mdx/Tsk double-mutant mice were then examined functionally, biochemically, and histologically. While mdx mice remained as strong as their normal counterparts, mdx/Tsk double-mutant mice became progressively weak with age. Serum creatine kinase activity was significantly elevated in both mdx and mdx/Tsk double-mutant mice over normal controls. However, mast cell-derived plasma tryptase activity was consistently higher in the double-mutant than in mdx mice. In addition, histological examination of gastrocnemius muscle revealed that while necrosis was persistent in both strains of mdx mice from 2 to 8 weeks of age, regeneration was significantly reduced in the double-mutant mice. Of particular interest was the fact that necrosis in the mdx/Tsk double mutant exceeded mdx values at 8 weeks of age, corresponding approximately with a second peak in tryptase activity. Therefore, heightened mast cell activity appears to elicit in the dystrophin-deficient mdx mouse a myopathy not unlike the human Duchenne disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chymases
  • Creatine Kinase / blood
  • Dystrophin / deficiency
  • Dystrophin / genetics
  • Female
  • Male
  • Mast Cells / metabolism
  • Mast Cells / physiology*
  • Mice
  • Mice, Mutant Strains
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Animal / genetics*
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / pathology
  • Mutation*
  • Necrosis / pathology
  • Phenotype
  • Serine Endopeptidases / blood
  • Skin / pathology
  • Tryptases

Substances

  • Dystrophin
  • Tpsb2 protein, mouse
  • Creatine Kinase
  • Serine Endopeptidases
  • chymase 2
  • Chymases
  • Tpsab1 protein, mouse
  • Tryptases