Equine exertional rhabdomyolysis (ER), often referred to as “tying-up”, is a clinical syndrome characterized by painful muscle contractures with exercise and skeletal muscle fiber necrosis. Thoroughbred horses are particularly susceptible to ER, with 5-10 % of all Thoroughbreds developing ER during a racing season. Thoroughbred horses with recurrent exertional rhabdomyolysis (RER) test negative for the GYS1 mutation associated with type 1 PSSM and the RYR1 mutation associated with MH. A diagnosis of RER is made on the basis of a history of recurring signs of muscle stiffness in association with high serum levels of the muscle enzymes creatine kinase (CK) and aspartate aminotransferase (AST) subsequent to muscle cell necrosis. The RER diagnosis is also supported by examination of a skeletal muscle biopsy, where histological features include an increased number of centrally located nuclei in mature muscle fibers and the absence of abnormal polysaccharide and excessive glycogen storage, which are characteristic of polysaccharide storage myopathy (PSSM).
There is strong evidence from earlier studies that RER susceptibility has an underlying genetic basis; however the genetic model and pattern of inheritance has not yet been conclusively defined. Estimations of RER heritability have been variable, which may reflect differences in RER diagnostic criteria or the contribution of many non-genetic factors. Such non-genetic risk factors include temperament, sex, age, diet, exercise routine, and the presence of lameness. Thoroughbreds with the greatest risk of developing RER are young, nervous females. We have scanned the horse genome with more than 48,000 single nucleotide polymorphisms (SNPs) in a search for genetic variants associated with RER in Thoroughbreds. Areas of the genome found to be strongly associated with RER are being investigated in further detail to better understand the genetic basis of this disease. It is unlikely that a single causative genetic mutation is responsible for RER susceptibility; rather, RER is likely a complex genetic disease resulting from one or more genes of major affect, as well as modifying genes, gender, and environmental factors.
This project was funded by Minnesota Agricultural Experiment Station, Morris Animal Foundation D07EQ-500, The University of Minnesota Equine Center, National Research Initiative Competitive Grant no. 2008-35205-18766 from the USDA National Institute of Food and Agriculture, NIH NIAMS 1K08AR055713-01A2, and NIH NIAMS T32-AR0076I2.
More information about clinical signs, diagnosis, and management of Recurrent Exertional Rhabdomyolysis (RER) and Exertional Rhabdomyolysis (ER) can be found as part of the Equine Neuromuscular Lab.
Fritz, K. L., McCue, M. E., Valberg, S. J., Rendahl, A. K. and Mickelson, J. R. (2012), Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbreds. Animal Genetics, 43: 730–738. doi: 10.1111/j.1365-2052.2012.02351.x