mdx mice show progressive weakness and muscle deterioration with age

Abstract

The time-course of degeneration/regeneration was investigated in leg muscles throughout the life of the mdx mutant mouse, which is a biochemical homologue of Duchenne muscular dystrophy (DMD). In young and adult mice (up to 52 weeks old), muscle fibre necrosis was compensated by a vigorous regeneration, but in old mdx mice (65-104 weeks) this regeneration slightly declined, while the necrotic process persisted. Body and muscles weights declined strikingly after 52 weeks. Life span of mdx mutants was reduced in comparison with the control C57BL/10 animals. Immunostaining of old mdx muscles showed clusters of dystrophin-positive fibres. Muscle fibres in old mdx mice showed great variation in size, many being atrophied or split. Endomysial fibrosis became increasingly 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 the murine and human diseases previously observed in diaphragm of mdx mice may be extended to other skeletal muscles.