Screening for a canine model of choroideremia exclusively identifies nonpathogenic CHM variants

Ophthalmic Res. 2011;45(3):155-63. doi: 10.1159/000313992. Epub 2010 Sep 23.

Abstract

Choroideremia is an X-linked, progressive photoreceptor degeneration disorder due to mutations in CHM. In addition to an atrophy of the outer retina, affected individuals present with a characteristic atrophy of the choroid. To search for a canine model, we screened the CHM gene of 37 dogs (22 breeds) with various forms of retinal dystrophies. We found 21 variations in 13 breeds (17 detected in only one breed and 4 shared by two or more) with 43% segregating in the same pedigree, a Great Dane female and a female offspring. Of particular interest were an exonic missense variation and a 3-bp intronic deletion near a splice acceptor site. However, although not detected in unrelated healthy Great Danes, these variants were nonpathogenic since they did not segregate with the disease phenotype in the pedigree. These results suggest that a CHM dog model may not be viable, as is the case for mouse and zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Choroideremia / genetics*
  • DNA Mutational Analysis
  • Disease Models, Animal*
  • Dogs
  • Female
  • Genetic Testing
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • rab GTP-Binding Proteins / genetics*

Substances

  • rab GTP-Binding Proteins