title: Screening for a canine model of choroideremia exclusively identifies nonpathogenic CHM variants.
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.
authors.affiliation: Inserm U-583, Institut des Neurosciences de Montpellier, Montpellier, France.
authors.forename: Lorenne
authors.initials: L
authors.lastname: Robert
authors.forename: Audrey
authors.initials: A
authors.lastname: Sénéchal
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.forename: Laetitia
authors.initials: L
authors.lastname: Herbin
authors.forename: Gilles
authors.initials: G
authors.lastname: Chaudieu
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kalatzis
authors.forename: Catherine
authors.initials: C
authors.lastname: André
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000818:Animals; D001483:Base Sequence; D015794:Choroideremia / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005820:Genetic Testing; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D020691:rab GTP-Binding Proteins