Causation for inherited equine night blindness

Abstract

Mutations associated with equine night blindness (CSNB) have been mapped to the Transient Receptor Potential cation channel family Member 1 (TRPM1) gene on ECA1. Reduced TRPM1 mRNA expression has been reported in retina and melanocytes in CSNB horses. A single unique intronic snp has been found in all CSNB horses examined to date. We hypothesize that this unique snp creates a binding site for the Nova intronic splicing enhancer which promotes aberrant splicing of an 80 bp downstream acceptor, therefore targeting TRPM1 mRNA for degradation. Nova‐1 and TRPM1 mRNA levels were measured in retina and in primary melanocyte cell lines established from the choroid of normal and CSNB horses. TRPM1 mRNA level in retina from a CSNB horse was 0.2% of that in the control horse retina. Choroidal melanocyes from normal and CSNB horses both had low TRPM1 mRNA levels similar to those observed in CSNB retina. We are investigating whether similar levels of TRPM1 mRNA in CSNB and normal melanocytes are due to removal of the effect of some upstream enhancer element in tissue culture, or result from insufficient Nova‐1 expression to cause the destabilizing TRPM1 mRNA splice event in CSNB melanocytes.Supported by the WCVM Canadian Vitamins Class Action Settlement Research Grant.