May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
A Conditional Knockout of AP-2 in the Developing Lens Results in an Isolated Ocular Phenotype Demonstrating an Intrinsic Requirement for AP-2 in the Lens and Eye Development
Author Affiliations & Notes
  • J. West-Mays
    Ophthalmology and Anatomy and Cell Biology, Tufts/New England Medical Center, Boston, MA, United States
  • S. Sullivan
    Depts. of CFB and CSB, University of Colorado Health Sciences Center, Denver, CO, United States
  • C. Dugan
    Ophthalmology, Tufts/New England Medical Center, Boston, MA, United States
  • R. Ashery-Padan
    Human Genetics and Molecular Medicine Sackler Faculty of Medicine,, Tel Aviv University, Ramat Aviv, Israel
  • P. Gruss
    Dept. of Molecular Cell Biology, Max-Planck-Institute of Biophysical Chemistry, Göttingen, Germany
  • T. Williams
    Dept. of Molecular Cell Biology, Max-Planck-Institute of Biophysical Chemistry, Göttingen, Germany
  • Footnotes
    Commercial Relationships  J. West-Mays, None; S. Sullivan, None; C. Dugan, None; R. Ashery-Padan, None; P. Gruss, None; T. Williams, None.
  • Footnotes
    Support  NIH EY11910 (JWM); P30 EY13078; RPB(JWM). NIH DE-12728 (TW).
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1070. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      J. West-Mays, S. Sullivan, C. Dugan, R. Ashery-Padan, P. Gruss, T. Williams; A Conditional Knockout of AP-2 in the Developing Lens Results in an Isolated Ocular Phenotype Demonstrating an Intrinsic Requirement for AP-2 in the Lens and Eye Development . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1070.

      Download citation file:


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

      ×
  • Supplements
Abstract

Abstract: : Purpose: We have previously shown that the AP-2α gene is a critical regulator of normal eye development since knockout mice in which the AP-2α gene has been deleted either completely lack eyes or have a mutant lens (ARVO 1998;2026). Since the AP-2α null mice have multiple craniofacial defects the possibility that these may have participated in the ocular phenotypes observed in the null mutant cannot be ruled out. In order to further address the specific function of AP-2α in defined tissue components of the eye, a conditional knockout of AP-2α in the developing lens has been created. Methods: A line of mice expressing Cre-recombinase specifically in the early lens placode (Le-Cre) was crossed with AP-2α flox’ed mice in which the AP-2α allele has been flanked by two loxP sites. Resultant Le-AP-2α mutant mice in which the AP-2α gene is only deleted in the developing lens were observed and compared to the full AP-2α knockout mice. Results: Post-natal Le- AP-2α mutant mice exhibited isolated ocular phenotypes including microphthalmia and lens defects. The deletion of AP-2α in the lens placode also caused some alterations in the craniofacial skeleton associated with the developing orbit. However, overall, the defects were restricted to the eye region and as a result a much more powerful model for studying the role of AP-2α in eye and lens development has been created. Conclusions: These data confirm that the AP-2α gene has an intrinsic role in early lens formation. The microphthalmia phenotype was also observed, as was reported in the AP-2α knockout mice, suggesting that this defect is caused by the extrinsic loss of signaling events dependent upon the expression of AP-2α in the lens. Further details regarding the specific nature of the lens and associated ocular phenotypes in the Le- AP-2α mutants and how they compare to the full knockout mice will be presented.

Keywords: transgenics/knock-outs • genetics • transcription factors 
×
×

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.

×