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