EVIDENCE OF MDX MOUSE SKELETAL-MUSCLE FRAGILITY IN-VIVO BY ECCENTRIC RUNNING EXERCISE

Duchenne muscular dystrophy is an X-linked devastating disease due to the lack of expression of a functional dystrophin. Unfortunately, the dystrophin-deficient mdx mouse model does not present clinical signs o f dystrophy before the age of 18 months, and the role of dystrophin in fiber integrity is not fully understood. The fragility of the skeleta l muscle fibers was investigated in transgenic mice expressing beta-ga lactosidase under the control of a muscle specific promoter. Adult mdx /beta-galactosidase (dystrophin-negative) and normal/beta-galactosidas e (dystrophin-positive) mice were submitted to one short session of ec centric, downhill running exercise. The leakage of muscle enzymes crea tine kinase and beta-galactosidase was investigated before, 1 h after, and 3 days after the running session. A significant and transient ris e in the level of these enzymes was noted in the serum of mdx mice fol lowing the exercise session. Thus, the lack of dystrophin in the mdx m odel led to local microdamages to the exercised muscle allowing leakag e of proteins from the fibers. The peak leakage was transient, suggest ing that muscle fiber lesions were rapidly repaired following this sho rt, noninvasive eccentric running session. (C) 1998 John Wiley & Sons, Inc.