Pig models for Duchenne muscular dystrophy - from disease mechanisms to validation of new diagnostic and therapeutic concepts.

Autor: Stirm M; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Fonteyne LM; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Shashikadze B; Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany., Stöckl JB; Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany., Kurome M; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Keßler B; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Zakhartchenko V; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Kemter E; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Blum H; Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany., Arnold GJ; Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany., Matiasek K; Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, 80539 Munich, Germany., Wanke R; Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, 80539 Munich, Germany., Wurst W; Institute of Developmental Genetics, Helmholtz Zentrum Munich, 85674 Neuherberg, Germany; Chair of Developmental Genetics, TUM School of Life Sciences, Technische Universität München, 85354 Freising, Germany., Nagashima H; Meiji University International Institute for Bio-Resource Research, 214-8571 Kawasaki, Japan., Knieling F; Pediatric Translational and Molecular Imaging Lab (PETI-Lab), University Hospital Erlangen, Department for Pediatrics and Adolescent Medicine, 91054 Erlangen, Germany., Walter MC; Friedrich Baur Institute, Department of Neurology, LMU Munich, 80336 Munich, Germany., Kupatt C; Klinik und Poliklinik für Innere Medizin I, Klinikum rechts der Isar, Technical University Munich and German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, 81675 Munich, Germany., Fröhlich T; Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany., Klymiuk N; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany., Blutke A; Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, 80539 Munich, Germany., Wolf E; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), Department of Veterinary Sciences, LMU Munich, 85764 Oberschleißheim, Germany; Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany. Electronic address: ewolf@genzentrum.lmu.de.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2022 Jul; Vol. 32 (7), pp. 543-556. Date of Electronic Publication: 2022 Apr 25.
DOI: 10.1016/j.nmd.2022.04.005
Abstrakt: Duchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the DMD gene, leading to complete absence of dystrophin and progressive degeneration of skeletal muscles and heart. Animal models are essential for preclinical evaluation of novel diagnostic procedures and treatment strategies. Gene targeting/editing offers the possibility of developing tailored pig models for monogenic diseases. The first porcine DMD model was generated by deletion of DMD exon 52 (DMDΔ52) in cultured kidney cells, which were used for somatic cell nuclear transfer to produce DMDΔ52 offspring. The animals resembled clinical, biochemical, and pathological hallmarks of DMD, but died before sexual maturity, thus preventing their propagation by breeding. This limitation was overcome by the generation of female heterozygous DMDΔ52 carrier pigs, which allowed the establishment of a large breeding colony. In this overview, we summarize how porcine DMD models have been used for dissecting disease mechanisms, for validating multispectral optoacoustic tomography as an imaging modality for monitoring fibrosis, and for preclinical testing of a CRISPR/Cas9 based approach to restore an intact DMD reading frame. Particular advantages of porcine DMD models include their targeted design and the rapid disease progression with early cardiac involvement, facilitating translational studies in reasonable time frames.
Competing Interests: Declarations of Competing Interest None
(Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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