title: Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.
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.
authors.affiliation: INRA, UMR703 APEX, Oniris, Atlantic Gene Therapies, Université de Nantes, Oniris, École nationale vétérinaire, agro-alimentaire et de l'alimentation, Nantes, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Larcher
authors.affiliation: INSERM, UMR 1087/CNRS 6291 Institut du Thorax, Université de Nantes, Faculté des Sciences et des Techniques, Nantes, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Lafoux
authors.affiliation: INSERM, UMR 1064-Center for Research in Transplantation and Immunology, ITUN, CHU Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tesson
authors.affiliation: INSERM, UMR 1064-Center for Research in Transplantation and Immunology, ITUN, CHU Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Remy
authors.affiliation: INSERM, UMR 1064-Center for Research in Transplantation and Immunology, ITUN, CHU Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Thepenier
authors.affiliation: 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.
authors.forename: Virginie
authors.initials: V
authors.lastname: François
authors.affiliation: 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.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Guiner
authors.affiliation: INRA, UMR703 APEX, Oniris, Atlantic Gene Therapies, Université de Nantes, Oniris, École nationale vétérinaire, agro-alimentaire et de l'alimentation, Nantes, France.
authors.forename: Helicia
authors.initials: H
authors.lastname: Goubin
authors.affiliation: INRA, UMR703 APEX, Oniris, Atlantic Gene Therapies, Université de Nantes, Oniris, École nationale vétérinaire, agro-alimentaire et de l'alimentation, Nantes, France.
authors.forename: Maéva
authors.initials: M
authors.lastname: Dutilleul
authors.affiliation: INRA, UMR703 APEX, Oniris, Atlantic Gene Therapies, Université de Nantes, Oniris, École nationale vétérinaire, agro-alimentaire et de l'alimentation, Nantes, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Guigand
authors.affiliation: INSERM, UMR 1087/CNRS 6291 Institut du Thorax, Université de Nantes, Faculté des Sciences et des Techniques, Nantes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Toumaniantz
authors.affiliation: INSERM, U1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: De Cian
authors.affiliation: INSERM, U1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Boix
authors.affiliation: INSERM, U1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Renaud
authors.affiliation: INRA, UMR703 APEX, Oniris, Atlantic Gene Therapies, Université de Nantes, Oniris, École nationale vétérinaire, agro-alimentaire et de l'alimentation, Nantes, France.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cherel
authors.affiliation: INSERM, U1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Giovannangeli
authors.affiliation: INSERM, U1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Concordet
authors.affiliation: INSERM, UMR 1064-Center for Research in Transplantation and Immunology, ITUN, CHU Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.affiliation: INSERM, UMR 1087/CNRS 6291 Institut du Thorax, Université de Nantes, Faculté des Sciences et des Techniques, Nantes, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Huchet
mesh_terms: D000818:Animals; D001483:Base Sequence; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D005355:Fibrosis; D017353:Gene Deletion; D015870:Gene Expression; D018390:Gene Targeting; D008297:Male; D018908:Muscle Weakness / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009137:Muscular Dystrophy, Animal; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D016189:Dystrophin; D012333:RNA, Messenger; D003402:Creatine Kinase