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Phenotype of dystrophinopathy in old mdx mice
J P Lefaucheur1, C Pastoret, A Sebille
1Laboratoire de Physiologie, Faculté de Médecine Saint-Antoine, Paris, France.
Background:
Mdx mutant mice, like patients with Duchenne Muscular Dystrophy (DMD), lack dystrophin, a subsarcolemmal protein, that results in myofiber necrosis. However young mdx mice, in contrast to DMD children, exhibit a successful muscle regeneration and not an extensive fibrosis.
Methods:
Old mdx mice were monitored clinically up to their spontaneous death, and most of their organs were studied histologically to look for differences with those of the wild C57BL/10 mice strain.
Results:
In old mdx mice (at least 20 months of age), we report clinical and pathological features of muscular dystrophy, i.e., progressive motor weakness and loss of myofibers replaced by extensive connective tissue, similar to the phenotype of dystrophinopathy observed in DMD patients. Various degrees of dystrophic involvement were observed in cardiac, respiratory, postural, and hindlimb skeletal mdx muscles and also in smooth muscles of the digestive and urinary tracts. No gross histological abnormalities were found in other tissue than muscular tissue.
Conclusions:
Late in life, mdx mice develop a muscular dystrophy close to DMD dystrophinopathy. We suggest that the study of the effects of ageing in mdx mice would give clues to better understand the pathophysiology of DMD.
Insights
Old mdx mice develop muscular dystrophy similar to Duchenne Muscular Dystrophy (DMD) patients, showing progressive weakness and fibrosis. Studying aging in mdx mice offers insights into DMD pathophysiology.
Area of Science:
- Biomedical research
- Animal models of human disease
- Muscle physiology
Background:
- Mdx mutant mice models lack dystrophin, similar to Duchenne Muscular Dystrophy (DMD) patients, leading to myofiber necrosis.
- Unlike DMD patients, young mdx mice typically show successful muscle regeneration without extensive fibrosis.
Purpose of the Study:
- To investigate the clinical and pathological features of muscular dystrophy in old mdx mice.
- To compare the phenotype of old mdx mice with that of wild-type mice and DMD patients.
Main Methods:
- Old mdx mice were monitored clinically until natural death.
- Histological examination of multiple organs was performed to identify differences compared to C57BL/10 wild-type mice.
Main Results:
- Old mdx mice (≥20 months) exhibited progressive motor weakness and myofiber loss, replaced by connective tissue, mirroring DMD dystrophinopathy.
- Dystrophic changes were observed in cardiac, respiratory, postural, and hindlimb skeletal muscles, as well as smooth muscles of the digestive and urinary tracts.
- No significant histological abnormalities were noted in non-muscular tissues.
Conclusions:
- Aging in mdx mice leads to a muscular dystrophy phenotype closely resembling DMD dystrophinopathy.
- Investigating the effects of aging in mdx mice can provide valuable insights into the pathophysiology of DMD.