Hindlimb immobilization applied to 21-day-oldmdx mice prevents the occurrence of muscle degeneration

Abstract

Dystrophin-deficient skeletal muscles of mdx mice undergo their first rounds of degeneration-regeneration at the age of 14–28 days. This feature is thought to result from an increase in motor activity at weaning. In this study, we hypothesize that if the muscle is prevented from contracting, it will avoid the degenerative changes that normally occur. For this purpose, we developed a procedure of mechanical hindlimb immobilization in 3-wk-old mice to restrain soleus (Sol) and extensor digitorum longus (EDL) muscles in the stretched or shortened position. After a 14-day period of immobilization, the striking feature was the low percentage of regenerated (centronucleated) myofibers in Sol and EDL muscles, regardless of the length at which they were fixed, compared with those on the contralateral side (stretched Sol: 8.4 ± 6.5 vs. 46.6 ± 10.3%, P = 0.0008; shortened Sol: 1.2 ± 1.6 vs. 50.4 ± 16.4%, P = 0.0008; stretched EDL: 05 ± 0.5 vs. 32.9 ± 17.5%, P = 0.002; shortened EDL: 3.3 ± 3.1 vs. 34.7 ± 11.1%, P = 0.002). Total numbers of myofibers did not change with immobilization. This study shows that limb immobilization prevents the occurrence of the first round of myofiber necrosis in mdx mice and suggests that muscle contractions play a role in the skeletal muscle degeneration of dystrophin-deficient mdx mouse muscles.