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H. Zhao, J. Rossant, D.M. Ornitz, D.C. Beebe, M.L. Robinson; Different FGFR Genes Play an Essential but Redundant Role in Post-Induction Lens Development . Invest. Ophthalmol. Vis. Sci. 2003;44(13):954.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Fibroblast growth factors (FGFs) can induce lens fiber differentiation in vivo and in vitro. FGFs function through binding and activation of FGF receptors (FGFRs). The developing lens expresses FGFR1, FGFR2 and FGFR3 genes in an overlapping but distinct pattern. Lens development is normal in FGFR3 null mice, and we showed that FGFR1 is independently dispensable for lens development. This study is to determine if FGFR2 or other combinations of FGFRs are required during lens development. Methods: FGFR3 null mice are viable and fertile, but null mutations in FGFR1 or FGFR2 are early embryonic lethal mutations. Therefore, we obtained mice carrying conditional mutations in both FGFR1 and FGFR2 that are activated by Cre recombinase. MLR10 transgenic mice express Cre in the lens from lens pit stage onward. Different combinations of FGFR mutations, with and without the Cre transgene, were generated by intercrossing. Lens total RNA was extracted from these mice and control littermates; RT-PCR and RNAse protection assay were performed to determine mRNA levels of different FGF receptors. Histological analysis was performed on the lens of these mice at different stages. Results: Mice with FGFR2 deleted specifically in lens are viable and fertile. RT-PCR and RNAse protection analyses determine that the deletion of FGFR2 in the lens is efficient and complete. Expression levels of FGFR1 and FGFR3 are not up regulated in these FGFR2 mutant mice. Lenses lacking FGFR2 appeared histologically normal. Also, the combined deletion of FGFR1 and FGFR3 does not appear to affect lens development, and mice deleted for FGFR2 and FGFR3 are not microphthalmic. However, preliminary analyses of mice with deletion of all three FGF receptors in the lens demonstrated that these mice have severe microphthalmia. Conclusions: No single FGFR gene is essential for post-induction lens development. However, deletion of all FGF receptor genes are not compatible with normal lens development. Therefore, individual FGFR genes play an essential yet redundant role in post-induction lens development.
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