Novel DMD mouse model carrying a multi-exonic Dmd deletion exhibit progressive muscular dystrophy and early-onset cardiomyopathy

Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular
disease caused by the lack of dystrophin, resulting in progressive muscle
wasting and locomotor dysfunctions. By adulthood, almost all patients also
develop cardiomyopathy, which is the primary cause of death in DMD. While
there has been extensive effort in creating animal models to study
treatment strategies for DMD, most fail to recapitulate the complete
skeletal and cardiac disease manifestations that are presented in affected
patients. Here, we generated a mouse model mirroring a patient deletion
mutation of exons 52-54 (Dmd &[Delta]52-54). The Dmd
&[Delta]52-54 mutation led to the absence of dystrophin, resulting
in progressive muscle deterioration with weakened muscle strength.
Moreover, Dmd &[Delta]52-54 present with early-onset
cardiomyopathy which is absent in current pre-clinical dystrophin
deficient mouse models. Therefore, Dmd &[Delta]52-54 presents
itself as an excellent pre-clinical model to evaluate the impact on
skeletal and cardiac muscles for both mutation dependent and independent
approaches.