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O.M. Medina, R. Berhinger, M. Jamrich; The role of the forkhead transcription factor Foxe3 In mouse Lens Development . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4537.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Foxe3 is a member of the fork–head/Fox family of transcription factors that is expressed the developing lens and the midbrain. During mouse lens development, Foxe3 is initially expressed in all the undifferentiated lens cells, but as the lens vesicle differentiates, the expression of Foxe3 becomes restricted to the cells of the anterior lens epithelium. Two mutations in the DNA binding forkhead domain of Foxe3 cosegregates with the dysgenetic lens (dyl) phenotype. In mice homozygous for dyl, the lens vesicle fails to close and separate from the cornea. In later stages of development, the lens epithelium does not proliferate properly. Although the mouse mutant dyl has been predicted to be a null allele of Foxe3, a convincing demonstration of the complete absence of Foxe3 function was lacking. To evaluate if the dyl phenotype is due to a complete loss of Foxe3 function, we have generated a null allele of Foxe3 by a targeted deletion of the entire coding region of this gene. Methods: We generated Foxe3–/– mice by a targeted deletion of the Foxe3 coding region. The phenotype of Foxe3–/– mice was analyzed by histology at different stages of lens development. Defects in lens development in Foxe3–/– embryos were investigated further by in situ hybridization using molecular markers expressed in the developing lens. Results: Mice carrying a Foxe3 null mutation are viable and fertile. The heterozygous mice show no abnormal phenotype. Homozygous null mice show obvious eye defects as early as 14 days postbirth. These mice have smaller eyes than the wild type animals. Some animals do not open their eyes at all. While the analysis of lens development at E12.5 and E14.5 showed similar phenotypes in dyl and Foxe3 –/– mice, at later stages there were clear differences between the two mutant strains. Conclusion: The Foxe3 –/– mutant mice differ in their lens phenotype from the dyl mice, suggesting that Foxe3 allele in the dyl mice is not a null allele.
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