Campus Units

Animal Science

Document Type

Article

Publication Version

Published Version

Publication Date

4-2014

Journal or Book Title

The FASEB Journal

Volume

28

Issue

4

First Page

1600

Last Page

1609

DOI

10.1096/fj.13-241141

Abstract

The purpose of this investigation was to determine the extent to which dystrophin insufficiency caused histomorphological changes in a novel pig model of Becker muscular dystrophy. In our procedures, we used a combination of biochemical approaches, including quantitative PCR and Western blots, along with a histological analysis using standard and immunohistological measures. We found that 8‐wk‐old male affected pigs had a 70% reduction in dystrophin protein abundance in the diaphragm, psoas major, and longissimus lumborum and a 5‐fold increase in serum creatine kinase activity compared with healthy male littermates. Dystrophin insufficiency in the diaphragm and the longissimus resulted in muscle histopathology with disorganized fibrosis that often colocalized with fatty infiltration but not the psoas. Affected animals also had an 80–85% reduction in α‐sarcoglycan localization in these muscles, indicating compromised assembly of the dystrophin glycoprotein complex. Controls used in this study were 4 healthy male littermates, as they are most closely related to the affected animals. We concluded that pigs with insufficient dystrophin protein expression have a phenotype consistent with human dystrophinopathy patients. Given that and their similarity in body size and physiology to humans, we further conclude that this pig line is an appropriate translational model for dystrophinopathies.—Hollinger, K., Yang, C. X., Montz, R. E., Nonneman, D., Ross, J. W., Selsby, J. T. Dystrophin insufficiency causes selective muscle histopathology and loss of dystrophin‐glycoprotein complex assembly in pig skeletal muscle.

Comments

This article is published as Hollinger, Katrin, Cai X. Yang, Robyn E. Montz, Dan Nonneman, Jason W. Ross, and Joshua T. Selsby. "Dystrophin insufficiency causes selective muscle histopathology and loss of dystrophin‐glycoprotein complex assembly in pig skeletal muscle." The FASEB Journal 28, no. 4 (2014): 1600-1609. doi: 10.1096/fj.13-241141.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf

Share

COinS