Longitudinal pathologic study of the gastrocnemius muscle group in mdx mice

Muscle necrosis in mdx mice is rare before the 2nd week of life, but becomes pronounced from weeks 2 to 6. There is no agreement on what happens after this age. Using sequential microscopic histology, immunohistochemistry and histomorphometry, we studied the evolution of muscle pathology throughout the mdx life span. Between 2 weeks and 3 months, multiple necrotic groups involving variable numbers of fibres were observed in the same section. During this period, most necrotic groups comprised more than 15 fibres. From 3 to 6 months, necrosis diminished progressively, involving isolated fibres or groups of two to five fibres, and most fibres had a centrally located nucleus. From 6 months onward there was progressive variation of fibre size and deposition of fibrillary collagens. Mast cell counts increased progressively until 6 months of age. Diminishing necrosis rather than increasing regeneration may explain the differences in muscle pathology observed between human DMD and mouse mdx. Mast cells play a secondary role in pathogenesis.