Document Type

Journal Article

Date of this Version

10-30-1998

Publication Source

Molecular Vision

Volume

4

Start Page

23

Abstract

Purpose: To clone and characterize the canine RPE65 cDNA from normal dog, examine for mutations, and establish if the mutation identified in Swedish briard dogs with retinal dystrophy is present in dogs of the same breed that originated from the United States and other countries, and are affected with congenital stationary night blindness.

Methods: Fifteen briard dogs were studied, of which 10 were affected with csnb, and five were clinically normal. In addition, we tested samples from four Swedish dogs, and samples from a briard affected with progressive retinal atrophy. RPE65 cDNA was cloned a from retinal cDNA library by PCR, and from canine retina by RT-PCR. ERG and morphology were used to characterize csnb.

Results: The normal RPE65 cDNA spans 1724 nucleotides (GenBank accession number AF084537), and includes 1602 nucleotides of coding sequence; the deduced amino acid sequence shares 98%, 97%, and 93% identity with homologous human, bovine, and rat sequences, respectively. A homozygous four nucleotide (AAGA) deletion, representing nucleotides 487-490 of wildtype RPE65 sequence, was found only in csnb and retinal dystrophy affected dogs; heterozygous animals had normal and mutant alleles. The mutation produces a frameshift, causing a deduced mistranslation with a premature stop codon. The mutation causes retinal dysfunction and RPE accumulation of lipid vacuoles.

Conclusions: Identification of the same mutation in csnb and retinal dystrophy confirms the molecular identity of the two disorders. A common mutation in dogs derived from different countries suggests a founder effect causing the propagation of a common mutant allele in the population at risk.

Copyright/Permission Statement

This paper was published by Molecular Vision under a CC BY-NC-ND 3.0 license.

Comments

PMID: 9808841

http://www.molvis.org/molvis/v4/p13

At the time of publication, author Gustavo Aguirre was affiliated with the James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University. Currently, he is a faculty member at the Vet Med school at the University of Pennsylvania.

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Date Posted: 12 November 2013

This document has been peer reviewed.