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Publication : Lifespan Analysis of Dystrophic <i>mdx</i> Fast-Twitch Muscle Morphology and Its Impact on Contractile Function.

First Author  Kiriaev L Year  2021
Journal  Front Physiol Volume  12
Pages  771499 PubMed ID  34950049
Mgi Jnum  J:324371 Mgi Id  MGI:6841815
Doi  10.3389/fphys.2021.771499 Citation  Kiriaev L, et al. (2021) Lifespan Analysis of Dystrophic mdx Fast-Twitch Muscle Morphology and Its Impact on Contractile Function. Front Physiol 12:771499
abstractText  Duchenne muscular dystrophy is caused by the absence of the protein dystrophin from skeletal muscle and is characterized by progressive cycles of necrosis/regeneration. Using the dystrophin deficient mdx mouse model, we studied the morphological and contractile chronology of dystrophic skeletal muscle pathology in fast-twitch Extensor Digitorum Longus muscles from animals 4-22 months of age containing 100% regenerated muscle fibers. Catastrophically, the older age groups lost approximately 80% of their maximum force after one eccentric contraction (EC) of 20% strain with the greatest loss of approximately 92% recorded in senescent 22-month-old mdx mice. In old age groups, there was minimal force recovery approximately 24% after 120 min, correlated with a dramatic increase in the number and complexity of branched fibers. This data supports our two-phase model where a "tipping point" is reached when branched fibers rupture irrevocably on EC. These findings have important implications for pre-clinical drug studies and genetic rescue strategies.
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