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Stirm, M.* ; Fonteyne, L.M.* ; Shashikadze, B.* ; Lindner, M.* ; Chirivi, M.* ; Lange, A.* ; Kaufhold, C.* ; Mayer, C.* ; Medugorac, I.* ; Kessler, B.* ; Kurome, M.* ; Zakhartchenko, V.* ; Hinrichs, A.* ; Kemter, E.* ; Krause, S.* ; Wanke, R.* ; Arnold, G.J.* ; Wess, G.* ; Nagashima, H.* ; Hrabě de Angelis, M. ; Flenkenthaler, F.* ; Kobelke, L.A.* ; Bearzi, C.* ; Rizzi, R.* ; Bahr, A.* ; Reese, S.* ; Matiasek, K.* ; Walter, M.C.* ; Kupatt, C.* ; Ziegler, S.* ; Bartenstein, P.* ; Fröhlich, T.* ; Klymiuk, N.* ; Blutke, A. ; Wolf, E.*

A scalable, clinically severe pig model for Duchenne muscular dystrophy.

Dis. Model. Mech. 14:dmm049285 (2021)
Postprint Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Large animal models for Duchenne muscular dystrophy (DMD) are crucial for evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) resemble molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/- carriers. A single founder animal had 11 litters with 29 DMDY/-, 34 DMD+/- as well as 36 male and 29 female wild-type offspring. Breeding with F1 and F2 DMD+/- carriers resulted in additional 114 DMDY/- piglets. With intensive neonatal management, the majority survived for 3-4 months, providing statistically relevant cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance of human disease mechanisms. Importantly, DMDY/- pigs reveal progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction already at age 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability. Our breeding cohort of DMDΔ52 pigs and standardized tissue repositories provide important resources for studying DMD disease mechanisms and for testing novel treatment strategies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Biobank ; Carrier ; Duchenne Muscular Dystrophy ; Pathology ; Pig Model ; Proteomics; Linkage Disequilibrium; Tomography; Perfusion; Modifier; Muscle
ISSN (print) / ISBN 1754-8403
e-ISSN 1754-8411
Journal Disease Models and Mechanisms
Quellenangaben Volume: 14, Issue: 12, Pages: , Article Number: dmm049285 Supplement: ,
Publisher Company of Biologists
Publishing Place Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Grants Else Kroener-Fresenius Foundation