Evaluation of Therapies to Enhance Muscle Function in Dysferlinopathies
The mouse models for dysferlin deficiency recapitulate the primary membrane-resealing defect in muscle. However, the disease progresses slowly, lengthening the time for evaluating any potential therapies. Histologic characterization has shown that the abdominal muscles of the A/J mouse provide the most severe pathology, yet this muscle (the rectus abdominus) is difficult to use for functional measurements due to its fiber geometry/architecture. Therefore, the goal of this study is to define a functional signature for the skeletal muscles in the A/J mouse over the course of 1 year. Isolated force measurements will be performed in the limb muscles (extensor digitorum longus (EDL) and soleus), and the diaphragm from 1 - 12 months of age. This will provide a solid basis for evaluating any potential therapies in terms of force generating capacity.