April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Effect Of Tissue-specific Disruption Of Porcupine On Mouse Eye Development
Author Affiliations & Notes
  • Sabine Fuhrmann
    Ophthal & Vis Sci,
    University of Utah, Salt Lake City, Utah
  • Mary P. Colasanto
    Ophthal & Vis Sci,
    University of Utah, Salt Lake City, Utah
  • Charles Murtaugh
    Human Genetics,
    University of Utah, Salt Lake City, Utah
  • Elizabeth J. Bankhead
    Ophthal & Vis Sci,
    University of Utah, Salt Lake City, Utah
  • Footnotes
    Commercial Relationships  Sabine Fuhrmann, None; Mary P. Colasanto, None; Charles Murtaugh, None; Elizabeth J. Bankhead, None
  • Footnotes
    Support  NIH/NEI EY014954, NIH/NEI Core Grant EY014800, unrestricted grant from Research to Prevent Blindness, Inc., to the Department of Ophthalmology, University of Utah
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 912. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sabine Fuhrmann, Mary P. Colasanto, Charles Murtaugh, Elizabeth J. Bankhead; Effect Of Tissue-specific Disruption Of Porcupine On Mouse Eye Development. Invest. Ophthalmol. Vis. Sci. 2011;52(14):912.

      Download citation file:

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

  • Supplements

Purpose: : During fetal development, the formation of the neural retina, retinal pigment epithelium (RPE) and anterior eye segment require highly coordinated tissue-tissue interactions and complex patterning events. The molecular signals that mediate these processes are not well understood. Excellent candidate signals are the Wnt ligands that control key processes during development and disease such as proliferation, cell fate decisions, tissue polarity and regeneration. The O-acyltransferase Porcupine (Porcn) is required for posttranslational modification regulating secretion and signaling activity of Wnts. PORCN deficiency in humans causes Focal Dermal Hypoplasia (FDH, Goltz Syndrome), an X-linked dominant multisystem birth defect that is frequently accompanied with ocular abnormalities resulting in coloboma, microphthalmia or, in severe cases, in anophthalmia. To gain insight into the contribution of canonical and non-canonical Wnt signaling during eye development, we are conditionally disrupting the Porcn gene in mouse.

Methods: : The conditional Porcn allele was generated by inserting loxP sites flanking exons 2-3. Thus, Cre-mediated recombination eliminates the start codon and the first 3 predicted transmembrane domains of the protein, likely producing a null or strong loss-of function allele. Porcn is disrupted in the developing mouse eye using tissue-specific Cre lines, and mutant eyes are analyzed by histological and immunohistochemical techniques.

Results: : Eye-specific disruption of Porcn results in defects with variable frequency, such as microphthalmia, coloboma and shortened presumptive ciliary body. Initial immunohistochemical analysis showed that Otx1/2 antibody labeling is detectable in mutant RPE using different ocular Cre lines. However, our preliminary data suggest that retina-specific disruption of Porcn causes transdifferentiation of the dorsal RPE into retina.

Conclusions: : Our studies indicate that expression of Porcn is critical for early eye development in mouse. Some of the observed defects are not detected upon interference with canonical Wnt signaling alone suggesting either a novel role for non-canonical Wnt signaling or a Wnt-independent function of Porcn during ocular development.

Keywords: gene/expression • retinal development • signal transduction 

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.