May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
AP–1 DNA Binding Activity in Retinas with RPGR Frame Shift Mutation
Author Affiliations & Notes
  • D. Gu
    Clinical Study, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • W.A. Beltran
    Clinical Study, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • G.M. Acland
    Clinical Study, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • S. Pearce–Kelling
    Baker institute, College of Veterinary Medicine, Cornell University, Ithaca, NY
  • G.D. Aguirre
    Clinical Study, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships  D. Gu, None; W.A. Beltran, None; G.M. Acland, None; S. Pearce–Kelling, None; G.D. Aguirre, None.
  • Footnotes
    Support  NIH– EY13132 and EY6855, The Foundation Fighting Blindness, the Van Sloun Fund for Canine Genetic Research.
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4576. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      D. Gu, W.A. Beltran, G.M. Acland, S. Pearce–Kelling, G.D. Aguirre; AP–1 DNA Binding Activity in Retinas with RPGR Frame Shift Mutation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4576.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : The AP–1 transcription factor plays an important role in regulating gene expression, and is activated in the process of photoreceptor degeneration. We examined the AP–1 DNA binding activity in affected retinas from dogs having a frameshift mutation of RPGR ORF15 to gain a better understanding of the molecular regulation of retinal degeneration.

Methods: : The retina tissue samples were collected from RPGR mutant dogs at 4, 6, 7, 9, 11 and 12 weeks, and the nuclear protein extracts were prepared. DNA binding activity of AP–1 was examined by electrophoretic mobility shift assay (EMSA). Retinal nuclear protein extracts from mutant dogs were hybridized with the labeled AP–1 consensus oligonucleotide, then analyzed with 2–20% gradient polyacrylamide gels. The AP–1 complex was detected as the shifted band, and the DNA binding activity of AP–1 was identified based on the intensity of the shifted bands.

Results: : Increased AP–1 DNA binding activity was identified in RPGR mutant dog retinas; the elevation of binding activity parallels the time course of photoreceptor degeneration.

Conclusions: : Analysis of retinal nuclear protein samples indicated that AP–1 DNA binding activity was induced in mutant dogs during the photoreceptor degeneration process. This result can support the hypothesis that increased AP–1 activity prior to and during apoptosis reflects increased expression of pro–apoptotic target genes. Further investigation on the induction of AP–1 DNA binding activity, the composition of the AP–1 protein complex, and the target genes transactivated by AP–1 will provide insights into the molecular mechanism of photoreceptor degeneration.

Keywords: transcription factors • retina • degenerations/dystrophies 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×