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

13 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.
LanguageEnglish
Pages1950-1957
JournalMolecular Therapy
Volume21
Issue number10
Early online date24 Sep 2013
DOIs
Publication statusE-pub ahead of print - 24 Sep 2013

Fingerprint

Muscular Dystrophies
Dystrophin
Stem Cells
Animal Models
Inbred mdx Mouse
Therapeutics
Heterografts
Natural Killer Cells
Protein Isoforms
B-Lymphocytes
Alleles
T-Lymphocytes

Keywords

  • murine model
  • human cell engrafment

Cite this

Vallese, Denis ; Negroni, Elisa ; Duguez, Stephanie ; Ferry, Arnaud ; Trollet, Capucine ; Aamiri, Ahmed ; Vosshenrich, Christian A J ; Füchtbauer, Ernst-Martin ; Di Santo, James P ; Vitiello, Libero ; Butler-Browne, Gillian ; Mouly, Vincent. / The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies. In: Molecular Therapy. 2013 ; Vol. 21, No. 10. pp. 1950-1957.
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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.",
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Vallese, D, Negroni, E, Duguez, S, Ferry, A, Trollet, C, Aamiri, A, Vosshenrich, CAJ, Füchtbauer, E-M, Di Santo, JP, 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, vol. 21, no. 10, pp. 1950-1957. https://doi.org/10.1038/mt.2013.186

The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies. / Vallese, Denis; Negroni, Elisa; Duguez, Stephanie; Ferry, Arnaud; Trollet, Capucine; Aamiri, Ahmed; Vosshenrich, Christian A J; Füchtbauer, Ernst-Martin; Di Santo, James P; Vitiello, Libero; Butler-Browne, Gillian; Mouly, Vincent.

In: Molecular Therapy, Vol. 21, No. 10, 24.09.2013, p. 1950-1957.

Research output: Contribution to journalArticle

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T1 - The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies

AU - Vallese, Denis

AU - Negroni, Elisa

AU - Duguez, Stephanie

AU - Ferry, Arnaud

AU - Trollet, Capucine

AU - Aamiri, Ahmed

AU - Vosshenrich, Christian A J

AU - Füchtbauer, Ernst-Martin

AU - Di Santo, James P

AU - Vitiello, Libero

AU - Butler-Browne, Gillian

AU - Mouly, Vincent

PY - 2013/9/24

Y1 - 2013/9/24

N2 - 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.

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KW - human cell engrafment

U2 - 10.1038/mt.2013.186

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M3 - Article

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SP - 1950

EP - 1957

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SN - 1525-0024

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