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Sci Rep. 2016 Sep 16;6:33362. doi: 10.1038/srep33362.

Progressive muscle proteome changes in a clinically relevant pig model of Duchenne muscular dystrophy.

Author information

1
Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
2
Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
3
Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Veterinärstr. 13, D-80539 Munich, Germany.
4
Friedrich-Baur-Institute, Department of Neurology, LMU Munich, Ziemssenstr. 1, D-80336 Munich, Germany.

Abstract

Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. We recently generated a novel genetically engineered pig model reflecting pathological hallmarks of human DMD better than the widely used mdx mouse. To get insight into the hierarchy of molecular derangements during DMD progression, we performed a proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and wild-type (WT) pigs. The extent of proteome changes in DMD vs. WT muscle increased markedly with age, reflecting progression of the pathological changes. In 3-month-old DMD muscle, proteins related to muscle repair such as vimentin, nestin, desmin and tenascin C were found to be increased, whereas a large number of respiratory chain proteins were decreased in abundance in DMD muscle, indicating serious disturbances in aerobic energy production and a reduction of functional muscle tissue. The combination of proteome data for fiber type specific myosin heavy chain proteins and immunohistochemistry showed preferential degeneration of fast-twitch fiber types in DMD muscle. The stage-specific proteome changes detected in this large animal model of clinically severe muscular dystrophy provide novel molecular readouts for future treatment trials.

PMID:
27634466
PMCID:
PMC5025886
DOI:
10.1038/srep33362
[Indexed for MEDLINE]
Free PMC Article

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