Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65

Genomics. 1999 Apr 1;57(1):57-61. doi: 10.1006/geno.1999.5754.


The RPE65 gene encodes a 65-kDa microsomal protein expressed exclusively in retinal pigment epithelium (RPE). Mutations in the human RPE65 gene have recently been identified in patients with autosomal recessive, severe, childhood-onset retinal dystrophy. Here we report the characterization of a 2.4-kb canine Rpe65 cDNA. The longest open reading frame predicts a 533-amino-acid protein with a calculated molecular mass of about 61 kDa prior to protein modification. Sequence comparison shows that RPE65 is highly conserved throughout mammalian evolution. We have identified a homozygous 4-bp deletion (485delAAGA) in putative exon 5 of the canine Rpe65 gene in affected animals of a highly inbred kinship of Swedish briard/briard-beagle dogs, in which an autosomal recessive, early-onset, and progressive retinal dystrophy segregates. The deletion results in a frameshift and leads to a premature stop codon after inclusion of 52 canine RPE65-unrelated amino acids from residue 153 onward. More than two-thirds of the wildtype polypeptide chain will be missing, and the mutant protein is most likely nonfunctional (null allele). Clinical features of the canine disease are quite similar to those described in human. Therefore this form of canine retinal dystrophy provides an attractive animal model of the corresponding human disorder with immediate significance for various therapeutic approaches, including RPE transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins
  • DNA Primers
  • Dog Diseases / genetics*
  • Dogs
  • Eye Proteins / genetics*
  • Molecular Sequence Data
  • Pedigree
  • Proteins*
  • Retinal Diseases / genetics*
  • Retinal Diseases / veterinary*
  • Sequence Analysis, DNA
  • Sequence Deletion*
  • cis-trans-Isomerases


  • Carrier Proteins
  • DNA Primers
  • Eye Proteins
  • Proteins
  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Associated data

  • GENBANK/Y16567