Progressive Proteome Changes in the Myocardium of a Pig Model for Duchenne Muscular Dystrophy
Hathaichanok Tamiyakul,
Elisabeth Kemter,
Miwako Kösters,
Stefanie Ebner,
Andreas Blutke,
Nikolai Klymiuk,
Florian Flenkenthaler,
Eckhard Wolf,
Georg J. Arnold,
Thomas Fröhlich
Affiliations
Hathaichanok Tamiyakul
Laboratory for Functional Genome Analysis, LAFUGA, Gene Center, LMU Munich, 81377 Munich, Germany
Elisabeth Kemter
Institute of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany
Miwako Kösters
Laboratory for Functional Genome Analysis, LAFUGA, Gene Center, LMU Munich, 81377 Munich, Germany
Stefanie Ebner
Institute of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany
Andreas Blutke
Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany
Nikolai Klymiuk
Institute of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany
Florian Flenkenthaler
Laboratory for Functional Genome Analysis, LAFUGA, Gene Center, LMU Munich, 81377 Munich, Germany
Eckhard Wolf
Laboratory for Functional Genome Analysis, LAFUGA, Gene Center, LMU Munich, 81377 Munich, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany; Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany; Corresponding author
Georg J. Arnold
Laboratory for Functional Genome Analysis, LAFUGA, Gene Center, LMU Munich, 81377 Munich, Germany; Corresponding author
Thomas Fröhlich
Laboratory for Functional Genome Analysis, LAFUGA, Gene Center, LMU Munich, 81377 Munich, Germany; Corresponding author
Summary: Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is characterized by progressive muscle weakness. Even though DMD manifests first in skeletal muscle, heart failure is a major cause of death in late-stage DMD. To get insights into DMD-associated cardiomyopathy, we performed a proteome analysis of myocardium from a genetically engineered porcine DMD model resembling clinical and pathological hallmarks of human DMD. To capture DMD progression, samples from 2-day- and 3-month-old animals were analyzed. Dystrophin was absent in all DMD samples, and components of the dystrophin-associated protein complex were decreased, suggesting destabilization of the cardiomyocyte plasma membrane and impaired cellular signaling. Furthermore, abundance alterations of proteins known to be associated with human cardiomyopathy were observed. Compared with data from skeletal muscle, we found clear evidence that DMD progression in myocardium is not only slower than in skeletal muscle but also involves different biological and biochemical pathways.
