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PLoS One. 2014 Oct 13;9(10):e110371. doi: 10.1371/journal.pone.0110371. eCollection 2014.

Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

Author information

1
INRA, UMR703 APEX, Oniris, Atlantic Gene Therapies, Université de Nantes, Oniris, École nationale vétérinaire, agro-alimentaire et de l'alimentation, Nantes, France.
2
INSERM, UMR 1087/CNRS 6291 Institut du Thorax, Université de Nantes, Faculté des Sciences et des Techniques, Nantes, France.
3
INSERM, UMR 1064-Center for Research in Transplantation and Immunology, ITUN, CHU Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
4
INSERM, UMR 1089, Atlantic Gene Therapies, Thérapie génique pour les maladies de la rétine et les maladies neuromusculaires, Université de Nantes, Faculté de Médecine, Nantes, France.
5
INSERM, UMR 1089, Atlantic Gene Therapies, Thérapie génique pour les maladies de la rétine et les maladies neuromusculaires, Université de Nantes, Faculté de Médecine, Nantes, France; Genethon, Evry, France.
6
INSERM, U1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.

Abstract

A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

PMID:
25310701
PMCID:
PMC4195719
DOI:
10.1371/journal.pone.0110371
[Indexed for MEDLINE]
Free PMC Article

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