title: Cloning and characterization of the canine photoreceptor specific cone-rod homeobox (CRX) gene and evaluation as a candidate for early onset photoreceptor diseases in the dog.
abstract: OBJECTIVE
  The cone-rod homeobox protein (CRX) is a member of the homeodomain-containing protein family expressed in the retinal photoreceptors and pinealocytes; it is involved in the regulation of the coordinate expression of multiple photoreceptor specific genes during retinal development. Mutations in the CRX gene are causally associated with retinal degeneration phenotypes in man. To clone the full length cDNA, characterize the genomic organization of canine CRX, map the gene in a radiation hybrid (RH) panel, and evaluate it as a candidate for canine inherited retinal degenerations.
  
  
  METHODS
  cDNA representational difference analysis (RDA) was done using normal and cone degeneration (cd) affected retinas. Exonic primers designed from consensus sequences of mammalian CRX cDNA were used to amplify and sequence dog genomic DNA. Canine specific primers were used for RH mapping of CRX on the RH3000 cell line. Linkage, sequencing and/or mapping the disease locus was used to evaluate CRX as a disease associated candidate gene.
  
  
  RESULTS
  The gene comprises three exons and two introns and codes for a transcript with a 900 bp open reading frame (ORF). In agreement with human map data, RH mapping placed canine CRX on the proximal end of CFA1, in a region of synteny with HSA19q13-q13.3. Based on RH mapping, meiotic linkage or sequencing data, we excluded CRX as the cause of canine early onset photoreceptor degenerations affecting Alaskan malamutes (cd), collies (rod-cone dysplasia 2, rcd2), American Staffordshire terriers, and Tibetan terriers.
  
  
  CONCLUSIONS
  Canine CRX has a high level of nucleotide and amino acid sequence identity with orthologous sequences reported for other species. The gene is excluded from causal association with 4 early onset photoreceptor diseases affecting cones (cd) or rods and cones (rcd2, PRA in American Staffordshire terriers, and Tibetan terriers).
authors.affiliation: Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA..
authors.forename: Novrouz B
authors.initials: NB
authors.lastname: Akhmedov
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Baldwin
authors.forename: Barbara
authors.initials: B
authors.lastname: Zangerl
authors.forename: James W
authors.initials: JW
authors.lastname: Kijas
authors.forename: Linda
authors.initials: L
authors.lastname: Hunter
authors.forename: Katayoun D
authors.initials: KD
authors.lastname: Minoofar
authors.forename: Cathryn
authors.initials: C
authors.lastname: Mellersh
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Acland
authors.forename: Debora B
authors.initials: DB
authors.lastname: Farber
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Aguirre
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002875:Chromosomes / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000032:analysis; D004285:Dogs / Q000235:genetics*; D005091:Exons; D015723:Gene Library; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D021101:Radiation Hybrid Mapping; D051381:Rats; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein