The Rag2⁻Il2rb⁻Dmd⁻ Mouse: a Novel Dystrophic and Immunodeficient Model to Assess Innovating Therapeutic Strategies for Muscular Dystrophies

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2013 Aug 27

PMID 23975040

Citations 12

Authors

Denis Vallese

Elisa Negroni

Stephanie Duguez

Arnaud Ferry

Capucine Trollet

Ahmed Aamiri

Christian A J Vosshenrich

Ernst-Martin Fuchtbauer

James P Di Santo

Libero Vitiello

Gillian Butler-Browne

Vincent Mouly

Affiliations

Soon will be listed here.

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.

Citing Articles

T cell biology in neuromuscular disorders: a focus on Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis.

Lemos J, Patricia Goncalves Tenorio L, Mouly V, Butler-Browne G, Mendes-da-Cruz D, Savino W Front Immunol. 2023; 14:1202834.

PMID: 37920473 PMC: 10619758. DOI: 10.3389/fimmu.2023.1202834.

Inflammasome Activity in the Skeletal Muscle and Heart of Rodent Models for Duchenne Muscular Dystrophy.

Onodi Z, Szabo P, Kucsera D, Pokreisz P, Dostal C, Hilber K Int J Mol Sci. 2023; 24(10).

PMID: 37239853 PMC: 10218525. DOI: 10.3390/ijms24108497.

Optimized lentiviral vector to restore full-length dystrophin via a cell-mediated approach in a mouse model of Duchenne muscular dystrophy.

Meng J, Moore M, Counsell J, Muntoni F, Popplewell L, Morgan J Mol Ther Methods Clin Dev. 2022; 25:491-507.

PMID: 35615709 PMC: 9121076. DOI: 10.1016/j.omtm.2022.04.015.

From Mice to Humans: An Overview of the Potentials and Limitations of Current Transgenic Mouse Models of Major Muscular Dystrophies and Congenital Myopathies.

Sztretye M, Szabo L, Dobrosi N, Fodor J, Szentesi P, Almassy J Int J Mol Sci. 2020; 21(23).

PMID: 33255644 PMC: 7728138. DOI: 10.3390/ijms21238935.

Efficient engraftment of pluripotent stem cell-derived myogenic progenitors in a novel immunodeficient mouse model of limb girdle muscular dystrophy 2I.

Azzag K, Ortiz-Cordero C, Oliveira N, Magli A, Selvaraj S, Tungtur S Skelet Muscle. 2020; 10(1):10.

PMID: 32321586 PMC: 7175515. DOI: 10.1186/s13395-020-00228-3.

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