A ROLE FOR MAST-CELLS IN THE PROGRESSION OF DUCHENNE MUSCULAR-DYSTROPHY - CORRELATIONS IN DYSTROPHIN-DEFICIENT HUMANS, DOGS, AND MICE

Dystrophin deficiency has been shown to be the underlying cause of Duc henne muscular dystrophy. Although dystrophin-deficient homologous ani mal models have been identified (dog, mouse, and cat), the clinical ex pression of the biochemical defect is species-specific. Thus, while th e genetics and biochemistry of Duchenne dystrophy is understood, the p athophysiological cascade leading to muscle weakness in only humans an d dogs remains obscure. To begin to dissect the pathophysiology at the histological level, we undertook a systematic study of mast cells in normal and dystrophin-deficient muscle. Mast cells have been implicate d in the development of fibrosis in other disorders, and progressive f ibrosis has been hypothesized to mediate the failure of muscle regener ation in human and dog dystrophin deficiency. Our results show a stron g correlation between mast cell content and localization, and the clin ico-histopathological progression in humans, dogs and mice. The mast c ell increases were disease specific: other dystrophic myopathies with normal dystrophin generally did not show substantial increases in mast cell content or degranulation. Our data suggest that mast cell accumu lation and degranulation may cause the grouped necrosis characteristic of dystrophin deficiency in all species.