Duchenne-like myopathy in double-mutant mdx mice expressing exaggerated mast cell activity.
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.
Granchelli
J A
JA
Department of Biological Sciences, University at Buffalo, NY 14260-1300, USA.
Pollina
C
C
Hudecki
M S
MS
D000818:Animals; D053818:Chymases; D003402:Creatine Kinase / Q000097:blood; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics; D005260:Female; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009336:Necrosis / Q000473:pathology; D010641:Phenotype; D012697:Serine Endopeptidases / Q000097:blood; D012867:Skin / Q000473:pathology; D053802:Tryptases
D016189:Dystrophin; C509190:Tpsb2 protein, mouse; D003402:Creatine Kinase; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C509222:Tpsab1 protein, mouse; D053802:Tryptases