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H Zhao, J Rossant, J Partanen, ML Robinson; FGFR1 Is Not Essential For Lens Fiber Cell Differentiation in Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2339.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Both in vivo and in vitro studies indicate that FGFs play an important role in mammalian lens fiber cell differentiation. The FGF receptors (FGFRs) are receptor tyrosine kinases that bind the FGFs and mediate their functions through intracellular signal transduction pathways. FGFR1 is expressed throughout lens development, and is essential for embryonic survival before lens induction. We have shown previously by the aphakia complementation system that FGFR1 null ES cells were capable of developing into embryonic lenses with normal morphology and normal crystallin expression pattern. As these chimeras do not survive to birth, we were unable to conduct further postnatal analysis of lens development in the absence of FGFR1. Therefore we utilized the Cre-lox P conditional knockout approach to selectively delete the FGFR1 gene in the lens to evaluate it's role in postnatal lens development and function. Methods:Mice harboring a conditional "floxed" mutation of FGFR1 were bred to a transgenic mouse line, MLR10, that expresses Cre recombinase in the entire lens under the control of a modified αA-crystallin promoter. These MLR10 mice were also heterozygous for a null mutation in FGFR1. A portion of the resulting progeny were both Cre positive and compound heterozygotes for null/floxed mutations in FGFR1. Adult mice and mouse embryos in which FGFR1 was deleted in the lens were collected for histological studies, proliferation analysis and gene expression analysis. Results:Mice with lens-specific deletion of FGFR1 were born without apparent developmental defects, and were found at the expected Mendelian ratio. In agreement with the results from aphakia complementation studies, the morphology of embryonic lens without FGFR1 was normal compared to wild type and heterozygous null littermate controls. Adult mice lacking FGFR1 in the lens were examined at the age of one and three months and exhibited normal ocular size and normal lens morphology. Conclusion:FGFR1 signaling is dispensable for normal lens development.
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