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

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.

Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1-associated canine retinal degeneration

“…In addition a slightly longer insert (ins69) was detected at the same position in Beagles (BE), including homozygous individuals (Miyadera et al 2009). A small study investigating RD in ESS from the US showed that out of six ins44 homozygous ESS dogs, four showed clinical signs, suggesting that an age of onset modifying locus may also play a role in development of RPGRIP1 associated disease in the ESS (Narfstrom et al 2012). In the same study investigation of Swedish ESS showed eight out of ten cases of RD in the ESS were not homozygous for the ins44 variant suggesting potential alternative clinical or genetic causes of RD in this breed.…”

Identification of Genetic Variants in <I>PDC, RHO, PDE6A</I> and <I>PDE6B</I> in Dogs with Progressive Retinal Atrophy

“…Canine eye disorder models can be used for human eye diseases and it has been proved invaluable in gene-therapy studies [16][17][18][19] . We have the opportunity to identify genetic variants associated with PRA in dogs as the canine genome sequences are readily accessible 20 . There are a number of retina-specific genes involved in the visual transduction pathway which are the candidate genes for PRA.…”

Progressive retinal atrophy in the Polski Owczarek Nizinny dog: a clinical and genetic study

“…18 The clinical characterization of specific forms of PRA is important to obtain reliable models for translational research. 13 The present report describes the phenotypic characteristics of a form of PRA in PON dogs and investigates the association with known PRA-causing gene mutations.…”

“…6 Typically, the association between the gene mutation and the development of PRA is straightforward, with most being fully penetrant, although occasionally the situation may appear to be more complex. [13][14][15][16] DNA-based tests are now available for several forms of PRA, 17 but the gene mutations underlying PRA in several dog breeds are still unknown. Because of genetic heterogeneity and the possibility of more than one form of PRA segregating within a breed, ophthalmic examinations of animals intended for breeding are very important, even in breeds where a DNA-based test for PRA is available.…”

“…At least 24 mutations in 18 genes have been associated with canine retinal disease . Typically, the association between the gene mutation and the development of PRA is straightforward, with most being fully penetrant, although occasionally the situation may appear to be more complex …”