دورية أكاديمية
A scalable, clinically severe pig model for Duchenne muscular dystrophy
| العنوان: | A scalable, clinically severe pig model for Duchenne muscular dystrophy |
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| المؤلفون: | Michael Stirm, Lina Marie Fonteyne, Bachuki Shashikadze, Magdalena Lindner, Maila Chirivi, Andreas Lange, Clara Kaufhold, Christian Mayer, Ivica Medugorac, Barbara Kessler, Mayuko Kurome, Valeri Zakhartchenko, Arne Hinrichs, Elisabeth Kemter, Sabine Krause, Rüdiger Wanke, Georg J. Arnold, Gerhard Wess, Hiroshi Nagashima, Martin Hrabĕ de Angelis, Florian Flenkenthaler, Levin Arne Kobelke, Claudia Bearzi, Roberto Rizzi, Andrea Bähr, Sven Reese, Kaspar Matiasek, Maggie C. Walter, Christian Kupatt, Sibylle Ziegler, Peter Bartenstein, Thomas Fröhlich, Nikolai Klymiuk, Andreas Blutke, Eckhard Wolf |
| المصدر: | Disease Models & Mechanisms, Vol 14, Iss 12 (2021) |
| بيانات النشر: | The Company of Biologists, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Pathology |
| مصطلحات موضوعية: | duchenne muscular dystrophy, pig model, pathology, proteomics, biobank, carrier, Medicine, Pathology, RB1-214 |
| الوصف: | Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit 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 an 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 to human disease mechanisms. Importantly, DMDY/− pigs displayed progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction, at 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1754-8403 1754-8411 |
| Relation: | http://dmm.biologists.org/content/14/12/dmm049285; https://doaj.org/toc/1754-8403; https://doaj.org/toc/1754-8411 |
| DOI: | 10.1242/dmm.049285 |
| URL الوصول: | https://doaj.org/article/d8939e99103646a0a9090e1ac2200524 |
| رقم الأكسشن: | edsdoj.8939e99103646a0a9090e1ac2200524 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17548403 17548411 |
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| DOI: | 10.1242/dmm.049285 |