title: 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.
authors: 1] UPMC Université Pierre et Marie Curie (UPMC), UM76, Institut de Myologie, Paris, France [2] INSERM U 974, Institut de Myologie, Paris, France [3] CNRS UMR 7215, Institut de Myologie, Paris, France [4] Department of Biology, University of Padova, Padova, Italy.
authors: Denis
authors: D
authors: Vallese
authors: Elisa
authors: E
authors: Negroni
authors: Stéphanie
authors: S
authors: Duguez
authors: Arnaud
authors: A
authors: Ferry
authors: Capucine
authors: C
authors: Trollet
authors: Ahmed
authors: A
authors: Aamiri
authors: Christian A J
authors: CA
authors: Vosshenrich
authors: Ernst-Martin
authors: EM
authors: Füchtbauer
authors: James P
authors: JP
authors: Di Santo
authors: Libero
authors: L
authors: Vitiello
authors: Gillian
authors: G
authors: Butler-Browne
authors: Vincent
authors: V
authors: Mouly
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics*; D055786:Gene Knockout Techniques; D006801:Humans; D007231:Infant, Newborn; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000235:genetics*; D009136:Muscular Dystrophies / Q000473:pathology* / Q000628:therapy; D009137:Muscular Dystrophy, Animal / Q000473:pathology* / Q000628:therapy; D032446:Myoblasts / Q000637:transplantation; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; D016189:Dystrophin; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; C499308:Rag2 protein, mouse; C085339:apo-dystrophin 1
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