The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies

Denis Vallese, Elisa Negroni, Stephanie Duguez, Arnaud Ferry, Capucine Trollet, Ahmed Aamiri, Christian A J Vosshenrich, Ernst-Martin Füchtbauer, James P Di Santo, Libero Vitiello, Gillian Butler-Browne, Vincent Mouly

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1950-1957
JournalMolecular Therapy
Volume21
Issue number10
Early online date24 Sep 2013
DOIs
Publication statusE-pub ahead of print - 24 Sep 2013

Keywords

  • murine model
  • human cell engrafment

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    Vallese, D., Negroni, E., Duguez, S., Ferry, A., Trollet, C., Aamiri, A., Vosshenrich, C. A. J., Füchtbauer, E-M., Di Santo, J. P., Vitiello, L., Butler-Browne, G., & Mouly, V. (2013). The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies. Molecular Therapy, 21(10), 1950-1957. https://doi.org/10.1038/mt.2013.186