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Christine Kerr, Trevor Williams, Judith West-Mays; AP-2α and AP-2β are Required for Normal Lens Development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):467.
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© ARVO (1962-2015); The Authors (2016-present)
The Activating Protein-2 (AP-2) family of transcription factors play crucial roles in the development of multiple tissues including the eye. AP-2α and AP-2β are co-expressed in the lens epithelium (LE) and cornea until E12.5, at which time AP-2β expression is lost from the LE. Using Le-AP-2α condition knockouts (KO), our lab has shown that AP-2α is required for proper lens development, and plays a critical role in the separation of the lens vesicle from the overlying surface ectoderm. Defects in the Le-AP-2α KOs were not seen until E12.5 when AP-2β expression is lost from the LE. In the current study, possible redundant roles of AP-2α and AP-2β in early stages of lens development were examined using a double conditional AP-2α/β KO mouse model.
AP-2α and AP-2β flox’ed mouse lines were mated with LeCre mice to conditionally delete AP-2α/β from the lens placode and its derivatives at E9.5. Eyes and lenses were examined at embryonic and postnatal stages using histological and immunofluorescent techniques.
The double conditional KO of AP-2α and AP-2β from the lens placode resulted in variable lens and eye phenotypes. At E13.5, the mutant lens is smaller than the WT and forms a lens stalk. At P4, mutants displayed microphthalmia with individual mutants often displaying variation in the size of one eye compared to the other. In severe cases, lenses were misplaced inside the optic cup with a disorganized and multilayered LE and denucleated fiber cells. A large mass of cells occupied space above the anterior region of the lens extending to the cornea. Abnormal corneal and retinal morphology was also evident. At P29, one mutant displayed bilateral anophthalmia. More moderate phenotypes at P4 included a small vacuolated lens with a lens stalk and abnormal corneal morphology. Pax6 was expressed correctly in the LE at E13.5, but its expression was expanded into the posterior of the lens at P4. Pax6 was not found to be expressed in the cell mass above the lens’ anterior region. β-Crystallin also appeared to be more highly expressed in mutants at E13.5 and P4.
Our studies reveal a requirement for AP-2α and AP-2β during lens development. A loss of both of these genes in early lens development results in a more severe phenotype than that seen in the single Le-AP-2α KOs, illustrating that both genes are necessary for proper lens development and may have redundant roles in early stages of lens development.
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