Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The DMDmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD), presenting the same molecular and protein defect. However, this mouse is not useful for clinical trials, because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene, and displays a severe phenotype. To help to elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein-complex in muscle sarcolemma, we generated double mutant mice for the dystrophin and LARGE proteins. The new DMDmdx/Largemyd mouse model is viable and shows a severe phenotype, associated to the lack of dystrophin in the muscle. We tested the usefulness of our new mouse model for cell therapy by systemically injecting them with normal murine mesenchymal adipose stem cells (mASC). We verified that the mASC were hosted in the dystrophic muscle. The new mouse model has proven to be very useful for the study of several other therapies, since injected cells can be screened both through DNA and protein analysis. Its significant weakness will also be very informative in the evaluation of functional benefits of these therapies.
- Received January 15, 2013.
- Accepted June 18, 2013.
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