Dis Model Mech. 2023 Dec 5:dmm.050395. doi: 10.1242/dmm.050395. Online ahead of print.
ABSTRACT
Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with fatal muscle degeneration and atrophy. Patients have progressive reductions in skeletal muscle strength and resistance to eccentric muscle stretch. We assessed tibiotarsal joint (TTJ) flexor and extensor force dynamics, and resistance of dystrophic muscle to eccentric stretch in the DE50-MD dog model of DMD. Male DE50-MD and WT dogs were analysed every 3 months until 18 months of age. There was an age-associated decline in eccentric contraction resistance in DE50-MD TTJ flexors that discriminated, with high statistical power, WT from DE50-MD individuals. For isometric contraction, at the majority of timepoints DE50-MD dogs had lower maximum absolute and relative TTJ flexor force, reduced TTJ muscle contraction times and prolonged relaxation compared to WT dogs. Cranial tibial muscles, the primary TTJ flexor, of 18-month-old DE50-MD dogs had significant numbers of regenerating fibres as expected, but also fewer type I fibres and more hybrid fibres than WT dogs. We conclude that these parameters, in particular the eccentric contraction decrement, could be used as objective outcome measures for pre-clinical assessment in DE50-MD dogs.
PMID:38050706 | DOI:10.1242/dmm.050395
