Skip to main content
ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Livestock Bio-Systems » Research » Publications at this Location » Publication #304232
Title: Dystrophin deficiency-induced changes in porcine skeletal muscle

Author
item Nonneman, Danny - Dan
item Rohrer, Gary
item ROSS, JASON - University Of Iowa
item HOLLINGER, KATRIN - University Of Iowa
item SELSBY, JOSH - University Of Iowa

Submitted to: American Meat Science Association Conference Reciprocal Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 5/15/2014
Publication Date: 6/20/2014
Citation: Nonneman, D., Rohrer, G., Ross, J.W., Hollinger, K., Selsby, J.T. 2014. Dystrophin deficiency-induced changes in porcine skeletal muscle. Proceedings of American Meat Science Association 67th Annual Reciprocal Meat Conference, June 15-18, 2014, Madison, Wisconsin. 4 pp. http://www.meatscience.org/publications-resources/rmc-proceedings

Interpretive Summary:

Technical Abstract: A novel porcine stress syndrome was detected in the U.S. Meat Animal Research Center’s swine research population when two sibling barrows died of apparent stress symptoms (open mouth breathing, vocalization, and refusal to move or stand) after transport at 12 weeks of age. At eight weeks of age, the piglets’ heart rates and electrocardiographs (ECG) were monitored during isoflurane challenge. Affected animals that reacted to isoflurane challenge also had elevated (three times higher) plasma creatine phosphokinase (CPK) before challenge and cardiac arrhythmias (abnormal ECG) during anesthesia. Of the forty-nine presumed affected pigs, based on isoflurane response, CPK levels, or assessment of their ECG, 18 died during isoflurane challenge. These animals showed signs of respiratory distress and a rapid decline in heart rate usually within one minute of anesthesia. Eight affected animals died a few days after challenge while being transported. A pedigree of 250 animals, including 49 affected pigs, was genotyped with the Illumina PorcineSNP60 beadchip and a single chromosomal region on the X chromosome (29-32 Mb) at the dystrophin locus was associated with the stress syndrome. Immunoblots of protein from cardiac or skeletal muscle showed a dramatic reduction (50-70%) in full-length dystrophin in affected pigs compared to their normal littermates at eight weeks and six months of age and a slight reduction in transcript levels by quantitative PCR. This reduction in dystrophin protein was also seen by immunohistochemistry in the longissimus lumborum, psoas, and diaphragm muscles. Histopathology of cardiac tissue showed a loss of cross-striation and pyknotic nuclei in myocardial fibers in affected pigs. Necrotic lesions with disorganized fibrosis, fatty infiltration, and aggregation of lymphocytes were found in diaphragm and longissimus muscles. The increased CPK, deficiency in dystrophin protein, and muscle lesions are consistent with dystrophinopathy in human patients and other animals. Dystrophin-associated glycoproteins alpha-sarcoglycan and alpha-dystroglycan levels were reduced in dystrophin deficient pigs, while desmin and laminin levels were unchanged. Utrophin, a protein orthologous to dystrophin that can compensate for loss of dystrophin, was not different in the dystrophin-deficient pigs. These studies indicate that dystrophin-deficient pigs have muscle injury and phenotypes that are consistent with human and model organism dystrophinopathies.