MDX MICE SHOW PROGRESSIVE WEAKNESS AND MUSCLE DETERIORATION WITH AGE

The time-course of degeneration/regeneration was investigated in leg m uscles throughout the life of the mdx mutant mouse, which is a biochem ical homologue of Duchenne muscular dystrophy (DMD). In young and adul t mice (up to 52 weeks old), muscle fibre necrosis was compensated by a vigorous regeneration, but in old mdx mice (65-104 weeks) this regen eration slightly declined, while the necrotic process persisted. Body and muscles weights declined strikingly after 52 weeks. Life span of m dx mutants was reduced in comparison with the control C57BL/10 animals . Immunostaining of old mdx muscles showed clusters of dystrophin-posi tive fibres. Muscle fibres in old mdx mice showed great variation in s ize, many being atrophied or split. Endomysial fibrosis became increas ingly conspicuous, and there was some accumulation of adipose tissue. These progressive degenerative changes of old mdx mice resemble those found in DMD and imply that basic pathological similarities between th e murine and human diseases previously observed in diaphragm of mdx mi ce may be extended to other skeletal muscles.