GENETIC STUDIES OF EQUINE MYOPATHIES

¹ Clinical and Population Sciences, University of Minnesota, College of Veterinary Medicine, 225 VTH, St. Paul, MN 55108 USA

² Veterinary Pathobiology, University of Minnesota, College of Veterinary Medicine, 295 AS/VM, St. Paul, MN 55108 USA

The first equine genomic test identified the point mutation in the skeletal muscle sodium channel gene that caused hyperkalemic periodic paralysis. One Quarter Horse stallion propagated this mutation to at least 60,000 offspring. A separate equine myopathy, commonly called tying-up or exertional rhabdomyolysis (ER) because of painful muscle cramping, has also been purported to be inherited. By carefully defining phenotypes of horses that developed muscle pain and rhabdomyolysis we have identified several breed-specific myopathies. One form of ER was characterized by glycogen and abnormal polysaccharide accumulation in muscle of related Appaloosa, Paint and Quarter Horses. The term polysaccharide storage myopathy was applied to this myopathy. Heritability was confirmed by breeding trials. A second form of ER, recurrent exertional rhabdomyolysis (RER), was identified in Thoroughbred horses. Intact intercostal muscle biopsies from RER horses showed lower contracture thresholds in response to caffeine and halothane in a fashion similar but not identical to malignant hyperthermia. Sixty Thoroughbreds with RER were all related to single founder. The contractile defect was also reproduced in offspring from affected mares. A third myopathy characterized by a distinctive globular polysaccharide in muscle was identified in young Quarter Horse foals that died from muscle weakness, hypoglycemic seizures and cardiomyopathy. Foals were deficient in glycogen branching enzyme and dams had decreased enzyme activity. Inheritance appeared to be autosomal recessive. In conclusion, many myopathies in horses appear to have a genetic basis. Development of a genome map in horses will facilitate the identification of the genetic defects responsible for these inherited disorders.