June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Large Animal Model of Autosomal Recessive RP due to a CNGB1 gene mutation
Author Affiliations & Notes
  • Simon Petersen-Jones
    Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI
  • Paige Winkler
    Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI
  • Joshua Bartoe
    Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI
  • Patrick Venta
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI
  • Kari Ekenstedt
    Department of Animal and Food Sciences, University of Wisconsin - River Falls, River Falls, WI
  • Footnotes
    Commercial Relationships Simon Petersen-Jones, None; Paige Winkler, None; Joshua Bartoe, None; Patrick Venta, None; Kari Ekenstedt, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 684. doi:
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      Simon Petersen-Jones, Paige Winkler, Joshua Bartoe, Patrick Venta, Kari Ekenstedt; Large Animal Model of Autosomal Recessive RP due to a CNGB1 gene mutation. Invest. Ophthalmol. Vis. Sci. 2013;54(15):684.

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      © ARVO (1962-2015); The Authors (2016-present)

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Several breeds of dog have recessively inherited retinal dystrophies making them potential large animal models of retinitis pigmentosa (RP). The purpose of this study was to investigate one such retinal dystrophy in the Papillon breed of dog.


A colony of Papillon dogs affected by an inherited progressive retinal degeneration was established. Affected dogs were phenotyped by ophthalmoscopic examination, vision testing and electroretinography. One dog was euthanized and the retina processed for immunohistochemistry. DNA samples were collected from colony dogs and privately owned Papillons with retinal degeneration and unaffected Papillons. 9 affected and 14 unaffected Papillon dogs were genotyped using a SNP microarray (Illumina Canine HD BeadChips).


The affected colony dogs had night-blindness from the earliest age that this could be assessed. Ophthalmoscopic signs of retinal thinning developed from between 12 and 18 months of age. The electroretinographic study revealed a marked reduction in rod-mediated responses from an early age. The SNP genotyping results from the affected colony dogs were compared with the control dogs and analyzed using a custom written program to detect regions of homozygozity in the affected dogs compared to the controls. Following additional microsatellite marker genotyping the cyclic nucleotide-gated channel beta 1 subunit (CNGB1) gene was identified as a positional candidate gene. The homozygous region surrounding CNGB1 was 1.84 Mb. Normal canine retinal cDNA and affected and control genomic DNA was sequenced. An exonic one-basepair deletion in CNGB1 predicted to result in a frame shift and premature stop codon was identified. This mutation segregated with the disease status in the colony dogs and was not present in the homozygous state in any unaffected dogs. Retinal immunohistochemistry showed a lack of labeling for CNGB1 in retinal sections from the affected dog whereas the antibody labeled rod outer segments in normal control dog retina.


A one-basepair deletion in CNGB1 in Papillon dogs causes a frame shift and premature stop codon, resulting in a lack of CNGB1 expression, markedly reduced or absent rod function, and a progressive retinal degeneration. This phenotype recapitulates the reported CNGB1 RP phenotype, making this dog colony a valuable large animal model for studying the effect of CNGB1 mutations and testing therapeutic intervention.

Keywords: 696 retinal degenerations: hereditary • 534 gene mapping • 510 electroretinography: non-clinical  

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