The Rag2 - Il2rb - Dmd - Mouse: A novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies

Abstract

The development of innovative therapeutic strategies for muscular dystrophies, particularly cell-based approaches, is still a developing field. Although positive results have been obtained in animal models, they have rarely been confirmed in patients and resulted in very limited clinical improvements, suggesting some specificity in humans. These findings emphasized the need for an appropriate animal model (i.e., immunodeficient and dystrophic) to investigate in vivo the behavior of transplanted human myogenic stem cells. We report a new model, the Rag2 - Il2rb - Dmd - mouse, which lacks T, B, and NK cells, and also carries a mutant Dmd allele that prevents the production of any dystrophin isoform. The dystrophic features of this new model are comparable with those of the classically used mdx mouse, but with the total absence of any revertant dystrophin positive fiber. We show that Rag2 - Il2rb - Dmd - mice allow long-term xenografts of human myogenic cells. Altogether, our findings indicate that the Rag2 - Il2rb - Dmd - mouse represents an ideal model to gain further insights into the behavior of human myogenic stem cells in a dystrophic context, and can be used to assess innovative therapeutic strategies for muscular dystrophies. © The American Society of Gene & Cell Therapy.