Postnatal changes in sarcolemmal organization in the mdx mouse

The tibialis anterior muscles of mdx mice degenerate between 3 and 4 weeks after birth and then partially recover. We show that the membrane cytoskeleton at the mdx sarcolemma is disorganized at 18-days postnatal, and becomes more disorganized at 4 weeks compared to earlier or later times. Mdx muscle at 18 days have few central nuclei, suggesting that it has not yet sustained significant damage. The variance of myofiber diameter confirms that the mdx pathology is greatest at 4 weeks, when the sarcolemma is most disorganized. Sarcolemmal disorganization in the mdx does not involve contractile structures, nor is it seen in age-matched controls. In revertant mdx fibers expressing dystrophin, sarcolemmal organization is similar to controls. Our results suggest that the absence of dystrophin results in the disorganization of the sarcolemma, even in 18-day-old mice, and that the extent of disorganization is greater when the myopathy is most severe.