ROLE OF THE ENDOTHELIN RECEPTOR B GENE IN OVERO COAT COLOR PATTERN AND LETHAL WHITE FOAL SYNDROME

¹ Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, 295 AS/VM, St. Paul, MN 5510 USA

² Clinical and Population Sciences, College of Veterinary Medicine, University of Minnesota, 225 VTH, St. Paul, MN 55108 USA

Overo coat color pattern in the horse is characterized by extensive white facial markings and patches of white coloration that do not cross the back between the withers and tail. Overo lethal white syndrome (OLWS) is an inherited syndrome of foals born to parents of overo lineage. Affected foals are totally or almost totally white, and die within days from complications due to intestinal aganglionosis. All OLWS foals are homozygous for an Ile118Lys mutation in the endothelin receptor B (EDNRB) gene, which is known to be involved in the developmental regulation of neural crest cells which ultimately become enteric ganglia and melanocytes. [125I]endothelin-3 binding experiments indicate that the content of functional EDNRB proteins in OLWS foal tissues is only 20% of that of control horses. If also true in neural crest cells during embryonic development, impaired EDNRB signaling function may directly lead to the OLWS phenotype. Overo horses can be phenotypically subclassified into several categories, the most common being frame and calico, and blending of white patterns is frequent. Frame overo characteristics are widespread in heterozygote parents of OLWS foals, but not all overo horses are heterozygous for the OLWS EDNRB mutation, indicating molecular heterogeneity of the overo pattern. The incidence of heterozygotes is >95% in frame and frame blend overos, but in calico overos varies greatly and is associated with the amount of white in the coat. Molecular definition of the frame overo pattern provides a genetic test for breeders and adds to our understanding of the basis for coat color patterns in the horse.