Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses.

Appaloosa horses are predisposed to equine recurrent uveitis (ERU), an immune-mediated disease characterized by recurring inflammation of the uveal tract in the eye, which is the leading cause of blindness in horses. Nine genetic markers from the ECA1 region responsible for the spotted coat color of Appaloosa horses, and 13 microsatellites spanning the equine major histocompatibility complex (ELA) on ECA20, were evaluated for association with ERU in a group of 53 Appaloosa ERU cases and 43 healthy Appaloosa controls. Three markers were significantly associated (corrected P-value <0.05): a SNP within intron 11 of the TRPM1 gene on ECA1, an ELA class I microsatellite located near the boundary of the ELA class III and class II regions and an ELA class II microsatellite located in intron 1 of the DRA gene. Association between these three genetic markers and the ERU phenotype was confirmed in a second population of 24 insidious ERU Appaloosa cases and 16 Appaloosa controls. The relative odds of being an ERU case for each allele of these three markers were estimated by fitting a logistic mixed model with each of the associated markers independently and with all three markers simultaneously. The risk model using these markers classified ~80% of ERU cases and 75% of controls in the second population as moderate or high risk, and low risk respectively. Future studies to refine the associations at ECA1 and ELA loci and identify functional variants could uncover alleles conferring susceptibility to ERU in Appaloosa horses.

Effect of diet on thoroughbred horses with recurrent exertional rhabdomyolysis performing a standardised exercise test.

Previous studies have associated recurrent exertional rhabdomyolysis (RER) with a diet high in soluble carbohydrate (CHO). The purpose of this study was to investigate the effect of 3 diets on clinical and metabolic parameters in 5 Thoroughbred horses with RER and 3 healthy Thoroughbreds performing a standardised exercise test (SET). Two diets were formulated to meet energy requirements for the amount of exercise being performed in the form of CHO or fat (21.4 Mcal DE/day). The third diet was formulated to provide 135% of the DE of the other 2 diets in the form of an excessive amount of carbohydrate (28.8 Mcal DE/day). Diets were fed in a crossover design for 3 week blocks and then horses performed a near maximal SET. Changes in heart rate (HR), plasma lactate, plasma glucose, total plasma solids, packed cell volume (PCV), muscle lactate and muscle glycogen concentration were measured immediately prior to, during, and 5 min after exercise. Serum creatine kinase (CK) activity was measured prior to and 4 h post SET. A 2-way ANOVA was used to examine the effect of group and dietary treatment. When dietary treatments were compared, horses fed the high-CHO diet had a mean pre-SET PCV and pre-SET HR that was higher than horses fed the fat diet (P = 0.06 and P = 0.07, respectively). Pre-SET heart rates were highest in RER horses consuming the high-CHO diet compared to RER horses consuming the low-CHO and fat diets (P = 0.02). Horses with RER had 4 h post SET CK activity greater than 400 u/l in 7/14 (50%) measurements compared to control horses which had CK activity greater than 400 u/l in 2/7 (29%) measurements. This study did not demonstrate a significant effect of diet on rhabdomyolysis, indicated by CK activity, or on the metabolic response to exercise. However, diet may have a calming effect on Thoroughbred horses with RER as manifested by decreased pre-exercise heart rates and decreased pre-exercise PCV in horses fed the fat diet.

Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.

Overo lethal white syndrome (OLWS) is an inherited syndrome of foals born to American Paint Horse parents of the overo coat-pattern lineage. Affected foals are totally or almost totally white and die within days from complications due to intestinal aganglionosis. Related conditions occur in humans and rodents in which mutations in the endothelin receptor B (EDNRB) gene are responsible. EDNRB is known to be involved in the developmental regulation of neural crest cells that become enteric ganglia and melanocytes. In this report we identify a polymorphism in the equine EDNRB gene closely associated with OLWS. This Ile to Lys substitution at codon 118 is located within the first transmembrane domain of this seven-transmembrane domain G-protein-coupled receptor protein. All 22 OLWS-affected foals examined were homozygous for the Lys118 EDNRB allele, while all available parents of affected foals were heterozygous. All but one of the parents also had an overo white body-spot phenotype. Solid-colored control horses of other breeds were homozygous for the Ile118 EDNRB allele. Molecular definition of the basis for OLWS in Paint Horses provides a genetic test for the presence of the Lys118 EDNRB allele and adds to our understanding of the basis for coat color patterns in the horse.