Assessment of Hereditary Retinal Degeneration in the English Springer Spaniel Dog and Disease Relationship to anRPGRIP1Mutation

Kristina Narfström,Richard W Madsen,Jennifer Hyman,Tomas F Bergström,Manbok Jeong

doi:10.1155/2012/685901

Abstract

Intensive breeding and selection on desired traits have produced high rates of inherited diseases in dogs. Hereditary retinal degeneration, often called progressive retinal atrophy (PRA), is prevalent in dogs with disease entities comparable to human retinitis pigmentosa (RP) and Leber's congenital amaurosis (LCA). Recent molecular studies in the English Springer Spaniel (ESS) dog have shown that PRA cases are often homozygous for a mutation in the RPGRIP1 gene, the defect also causing human RP, LCA, and cone rod dystrophies. The present study characterizes the disease in a group of affected ESS in USA, using clinical, functional, and morphological studies. An objective evaluation of retinal function using electroretinography (ERG) is further performed in a masked fashion in a group of American ESS dogs, with the examiner masked to the genetic status of the dogs. Only 4 of 6 homozygous animals showed clinical signs of disease, emphasizing the need and importance for more precise studies on the clinical expression of molecular defects before utilizing animal models for translational research, such as when using stem cells for therapeutic intervention.

Highlights

The domestic dog has a unique population history with bottlenecks that has shaped the diversity and structure of the canine genome
This paper describes the results of a research project that was thereafter initiated, in order to characterize the clinical signs of retinal degeneration in the English Springer Spaniel (ESS) breed and to evaluate the genotype-phenotype correlation in USA in family-owned ESS, in regards to the mutation in the RPGRIP1 gene
At this stage there was decoloration interspersed with hyperpigmentation of the nontapetal fundus

Summary

Introduction

The domestic dog has a unique population history with bottlenecks that has shaped the diversity and structure of the canine genome. The presence of more than one causative mutation for PRA in some breeds is complicating the understanding and interpretation of phenotype-genotype relationships and the results of DNA testing procedures [12] Due to these factors, phenotypic heterogeneity is often found when studying various forms of retinal degenerative diseases of dogs. The RPGRIP1 mutation in cone rod dystrophy (cord1) was further evaluated as a candidate gene for PRA in ESS dogs using DNA collected at the University of Missouri (Columbia, USA), from a large number of dogs, unaffected and affected by bilateral, generalized retinal degeneration. This paper describes the results of a research project that was thereafter initiated, in order to characterize the clinical signs of retinal degeneration in the ESS breed and to evaluate the genotype-phenotype correlation in USA in family-owned ESS, in regards to the mutation in the RPGRIP1 gene. Without clinical signs of PRA and the correlation in regards to the RPGRIP1 mutation

Materials and Methods

Results

Discussion