Recurrent exertional rhabdomyolysis (RER, tying-up) causes affected Thoroughbreds to suffer recurring episodes of muscle cramping, stiffness, excessive sweating, and a reluctance to move after exercise. With no cure available, information on how RER might be inherited is welcome news to the Thoroughbred industry.
James Mickelson, PhD, professor of biochemistry at the University of Minnesota College of Veterinary Medicine, summarized the study, which recently appeared in the Journal of the American Veterinary Medical Association. "We know that RER is influenced by gender, temperament, and diet, among other factors," said Mickelson. "We now believe that RER is also a genetic trait with an inheritance pattern indistinguishable from autosomal dominant (requires that only one affected parent have the trait to pass it to offspring)." Previous studies reported that muscle biopsies from RER horses are abnormally sensitive to chemicals that stimulate muscle contraction, such as caffeine and the anesthetic halothane. Mickelson and colleagues used this abnormality of RER muscle to design a diagnostic test for RER using thin strips of muscle from Thoroughbreds with and without the disease.
"The test was intended only as a research tool," Mickelson says. "The muscle dissection and measurements are too time-consuming and complex to make it clinically useful. Still, the muscle contracture test allowed us to eliminate variables such as diet, training regimes, and other confounding influences on the expression of RER...and focus on what goes wrong in RER muscle, in a controlled laboratory setting."
Mickelson's group wanted to use this test to determine how RER is inherited. Horses of known RER status, most of which were diagnosed with the muscle contracture test, were mated to produce 23 foals. (An RER stallion, the son of an RER-positive mare and a healthy stallion, was bred to five healthy mares to produce the 23 foals.) Of these, five of 12 colts and four of 11 fillies tested RER-positive. Using simple segregation analysis, scientists determined whether affected offspring "segregated" (divided) into expected proportions for each parental pairing. With autosomal dominant traits, if only one parent is affected, that parent carries one copy of the affected gene and there is a 50% chance of producing affected offspring. If both parents are affected, both parents carry one copy of the affected gene and there is a 75% chance of producing affected offspring. Statistically, the results ruled out X-linked (a trait traveling with the X chromosome) and autosomal recessive patterns, and supported an autosomal dominant mode of inheritance.
The RER gene will need to be identified and sequenced before RER is truly understood. "We are scanning the equine genome from RER pedigrees using DNA markers to attempt to find which chromosome the RER gene lies on," says Mickelson. "Ideally, we just may find this chromosome--and possibly the gene itself--within two to three years."
Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.