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- W2891961250 abstract "The evaluation of muscle function is an important part of pre-clinical testing of novel treatments for muscular dystrophies. However, muscle pathology in the most commonly used mouse model of Duchenne muscular dystrophy (DMD), the mdx mouse, is less severe than that in DMD patients and most protocols only evaluate maximal isometric force (Fmax). In contrast, mdx mice on a DBA/2 background show significant muscle atrophy and may therefore be a better model of DMD pathology. We measured the force-frequency relationship, fatigue resistance during isotonic contractions at 30% of Fmax and resistance to eccentric contractions (ECC) in situ in the triceps surae (TS) of mdx and control mice on a BL/10 (5 m/o) or DBA/2 (3 m/o) background. In BL/10 mdx mice, Fmax was decreased compared to control mice (-17%), even though TS mass was increased (+50%). Specific force was decreased by 40-47% across the stimulation frequencies. Fatigue resistance was not different, but force recovery from fatigue was worse in mdx mice. In DBA/2 mdx mice the deficit in specific force was less (22-28%), but the deficit in Fmax was larger (-43%) compared to BL/10 mice due to muscle weight loss (-27%). Unexpectedly, fatigue recovery was better in mdx mice and we found no deficit during ECC. Dystrophin exon skipping was induced in a group of BL/10 mdx mice with antisense PMO. PMO treatment only improved specific force at high stimulation frequencies and the force deficit during ECC was only partially recovered. Force recovery from fatigue was normalised and muscle work during the protocol was increased. We believe it's important to evaluate muscle function during submaximal and dynamic muscle contractions and that our isotonic contraction protocol better resembles muscle usage in vivo. We suggest that the large deficit in specific force and the reduced recovery from fatigue of BL/10 mdx TS in situ might allow for the sensitive detection of the effects of novel therapies for DMD on muscle function." @default.
- W2891961250 created "2018-09-27" @default.
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- W2891961250 date "2018-10-01" @default.
- W2891961250 modified "2023-09-25" @default.
- W2891961250 title "DMD TREATMENT: ANIMAL MODELS" @default.
- W2891961250 doi "https://doi.org/10.1016/j.nmd.2018.06.245" @default.
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