A defect in dystrophin causes a novel porcine stress syndrome

Authors: Nonneman, Danny - Dan; Brown-Brandl, Tami; Jones, Shuna; Wiedmann, Ralph; Rohrer, Gary

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/25/2012
Publication Date: 6/12/2012
Citation: Nonneman, D.J., Brown-Brandl, T., Jones, S.A., Wiedmann, R.T., Rohrer, G.A. 2012. A defect in dystrophin causes a novel porcine stress syndrome. Biomed Central (BMC) Genomics. 13:233.

Interpretive Summary: Losses of slaughter-weight pigs due to transport stress are both a welfare and an economic concern to pork producers. We identified two sibling barrows in the USMARC swine herd that died from apparent symptoms of a stress syndrome after transport to a research location at 12 weeks of age. The symptoms included open-mouth breathing, skin discoloration, vocalization and loss of mobility. We repeated the original mating along with sire-daughter matings to produce additional offspring and at 8 weeks of age, pigs were challenged with isoflurane anesthesia to produce a stress response. Affected animals had cardiac arrhythmias, as determined by electrocardiographs. Additional animals from six other litters were identified as having a stress response, sometimes resulting in death, during regular processing and weighing. Using high-density genotyping we were able to map the abnormal stress response to the dystrophin gene on the X chromosome. Heart and skeletal muscle showed a dramatic reduction of dystrophin protein in affected animals and affected hearts displayed muscle fiber degeneration. In humans, mutations in dystrophin cause weak abnormal muscle development and enlarged, weak hearts. The identification of the causative mutation in these families will allow the investigation of the prevalence and subsequent elimination of this condition in commercial swine populations and provide a unique biomedical model for similar human diseases.

Technical Abstract: Two sibling barrows were identified in the USMARC swine herd that died from apparent symptoms of a stress syndrome after transport to a research location at 12 weeks of age. The symptoms included open-mouth breathing, skin discoloration, vocalization and loss of mobility. The original mating was repeated, along with sire-daughter matings to produce additional offspring. At 8 weeks of age, pigs were challenged with isoflurane anesthesia (3% for 3 min) and heart rate and electrocardiographs (ECG) were monitored during anesthesia. Four males from the original sire-dam mating and two males from a sire-daughter mating died after one minute of anesthesia. Additional animals in the herd were identified as having a stress response, sometimes resulting in death, during regular processing and weighing. Affected animals had elevated plasma creatine phosphokinase (CPK) levels before and immediately after isoflurane challenge and cardiac arrhythmias, as determined by ECG. A pedigree containing 250 pigs, including 49 affected animals, were genotyped with the Illumina Porcine 60K SNP Beadchip and one chromosomal region, SSCX at 25.1-27.7 Mb over the dystrophin gene, was significantly associated with the syndrome. An arginine to tryptophan (R1958W) polymorphism in exon 41 of the dystrophin gene was the most significant marker associated with stress susceptibility. Immunoblots of heart and skeletal muscle showed a dramatic reduction of dystrophin protein in affected animals and histopathology of affected hearts indicated muscle fiber degeneration. Therefore, the causative genetic factor for this novel stress syndrome most likely resides within the dystrophin gene and results in less dystrophin protein and cardiac abnormalities that can lead to death under stressful situations. The identification of the mutation will allow us to determine the prevalence of this disease in commercial swine populations.