Age-related changes in collagen gene expression in the muscles of mdx dystrophic and normal mice.

It has been shown that there is a marked accumulation of collagen (notably type III) in the muscles of Duchenne muscular dystrophy patients. Although not as marked, there is also an accumulation of collagen in normal skeletal muscle with age. To attempt to determine whether dystrophy-related and/or age-related collagen accumulation are the result of increased collagen gene expression, sections from muscles of mdx and control mice at different ages were subjected to in situ hybridization with cRNA probes for procollagen I and III to estimate changes in specific mRNA levels. Greater amounts of collagen I and III mRNA were noted in skeletal muscles and the diaphragm of the mdx mice than in the same muscles of age matched controls. The over-expression of these collagen genes was particularly noticeable in the mdx diaphragm and may possibly be explained by the greater activity of this muscle as compared to the limb muscles of these dystrophic mice. There was, however, an age-related decline of collagen expression in both normal and dystrophic muscle and this strongly suggests that the increased fibrosis of skeletal muscle with age is not the result of increased collagen gene expression but is most likely due to an impairment of degradation. In contrast, the excess accumulation of collagen in dystrophic muscle compared to normal muscle is related to increased gene expression, probably triggered by an injured tissue response induced by muscle fibre damage due to the lack of dystrophin.