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CM Garcia, J Guo, ME Gross, K Yu, R Ashery-Padan, P Gruss, DM Ornitz, DC Beebe; Targeted Deletion of FGF Receptor-2 Identifies a Role for FGF Signaling in Lens Growth . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2338.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Fibroblast growth factors (FGFs) are implicated in lens development, mainly in the differentiation of fiber cells. We examined the role of FGF signaling during lens development using the Cre/loxP system to disrupt the gene for FGF receptor-2 (FR2) in the lens placode and prospective corneal and conjunctival epithelia. Methods:Mice expressing Cre recombinase driven by the Pax6 P0 promoter were mated with mice in which the FR2 gene was flanked by loxP sequences. Progeny were genotyped using PCR and mice heterozygous for Cre and FR2-loxP were mated to obtain mice that were FR2+/+, FR2+/loxP, or FR2loxP/loxP. Eyes from embryos and adults were prepared for histological examination. Results:At all stages, the eyes of mice that are FR2+/loxP or FR2loxP/loxP but do not express Cre, appear normal. In Cre-positive animals, targeted deletion of the FR2 gene leads to a delay in lens vesicle formation at E10.5. The lens vesicle is closed and primary fibers are elongating in FR2+/+ and FR2+/loxP, but not in FR2loxP/loxP embryos. At E13.5, FR2loxP/loxP animals have a reduced number of epithelial cells compared to embryos with at least one wild type FR2 allele, although the primary fiber cells appear morphologically normal. At E17.5, eyelid closure is delayed and the lenses are smaller in FR2loxP/loxP than in FR2+/+ and FR2+/loxP embryos. Some lenses appear morphologically normal, while others have a disproportionately small number of lens epithelial cells. Adult FR2loxP/loxP mice have fused eyelids and small eyes. The retina is folded and the lens is fragmented or absent. Conclusion:FR2 is not required for lens induction or the formation of lens epithelial or primary fiber cells. From these preliminary observations, the major function of FR2 appears to be in lens epithelial cell growth and/or survival. FR2 also plays an important role in the development of the ocular surface epithelia. CR: None. Support: Research to Prevent Blindness, EY04853 and core grant EY02687
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