neurogenetics

, Volume 11, Issue 2, pp 163–174

Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene

Authors

    • Department of Human GeneticsRuhr-University Bochum
  • Conni Vollrath
    • Department of Human GeneticsRuhr-University Bochum
  • Elisabeth Petrasch-Parwez
    • Department of Neuroanatomy and Molecular Brain ResearchRuhr-University Bochum
  • Michael H. Boevé
    • Department of Clinical Sciences of Companion Animals, Faculty of Veterinary MedicineUniversity of Utrecht
  • Denis A. Akkad
    • Department of Human GeneticsRuhr-University Bochum
  • Wanda M. Gerding
    • Department of Human GeneticsRuhr-University Bochum
  • Jörg T. Epplen
    • Department of Human GeneticsRuhr-University Bochum
ORIGINAL ARTICLE

DOI: 10.1007/s10048-009-0223-z

Cite this article as:
Dekomien, G., Vollrath, C., Petrasch-Parwez, E. et al. Neurogenetics (2010) 11: 163. doi:10.1007/s10048-009-0223-z

Abstract

Canine generalized progressive retinal atrophy (gPRA) is characterized by continuous degeneration of photoreceptor cells leading to night blindness and progressive vision loss. Until now, mutations in 11 genes have been described that account for gPRA in dogs, mostly following an autosomal recessive inheritance mode. Here, we describe a gPRA locus comprising the newly identified gene coiled-coil domain containing 66 (CCDC66) on canine chromosome 20, as identified via linkage analysis in the Schapendoes breed. Mutation screening of the CCDC66 gene revealed a 1-bp insertion in exon 6 leading to a stop codon as the underlying cause of disease. The insertion is present in all affected dogs in the homozygous state as well as in all obligatory mutation carriers in the heterozygous state. The CCDC66 gene is evolutionarily conserved in different vertebrate species and exhibits a complex pattern of differential RNA splicing resulting in various isoforms in the retina. Immunohistochemically, CCDC66 protein is detected mainly in the inner segments of photoreceptors in mouse, dog, and man. The affected Schapendoes retina lacks CCDC66 protein. Thus this natural canine model for gPRA yields superior potential to understand functional implications of this newly identified protein including its physiology, and it opens new perspectives for analyzing different aspects of the general pathophysiology of gPRA.

Keywords

CCDC66 geneInsertion mutationGeneralized progressive retinal atrophyRetinal protein expressionCCDC66 immunohistochemistry

Supplementary material

10048_2009_223_MOESM1_ESM.doc (352 kb)
Supplementary Table 1a: Oligonucleotides used for mutation screening, DNA sequencing, splicing, cloning and qRT-PCR analyses in dog and mouse. *#: Oligonucleotides were also used for splice analysis (DOC 352 kb)
10048_2009_223_MOESM2_ESM.doc (60 kb)
Supplementary Table 2b: Oligonucleotides used for linkage analysis and fine mapping of the candidate region. F primers were tailed using the unique sequence CAT CGC TGA TTC GCA for HEX or FAM labeling needed for genotyping analyses (DOC 60 kb)

Copyright information

© Springer-Verlag 2009