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Simon A. Chanas, J. Martin Collinson, Thaya Ramaesh, Natalie Dorà, Dirk A. Kleinjan, Robert E. Hill, John D. West; Effects of Elevated Pax6 Expression and Genetic Background on Mouse Eye Development. Invest. Ophthalmol. Vis. Sci. 2009;50(9):4045-4059. doi: 10.1167/iovs.07-1630.
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purpose. To analyze the effects of Pax6 overexpression and its interaction with genetic background on eye development.
methods. Histologic features of eyes from hemizygous PAX77 +/− transgenic (high Pax6 gene dose) and wild-type mice were compared on different genetic backgrounds. Experimental PAX77 +/−↔wild-type and control wild-type↔wild-type chimeras were analyzed to investigate the causes of abnormal eye development in PAX77 +/− mice.
results. PAX77 +/− mice showed an overlapping but distinct spectrum of eye abnormalities to Pax6 +/− heterozygotes (low Pax6 dose). Some previously reported PAX77 +/− eye abnormalities did not occur on all three genetic backgrounds examined. Several types of eye abnormalities occurred in the experimental PAX77 +/−↔wild-type chimeras, and they occurred more frequently in chimeras with higher contributions of PAX77 +/− cells. Groups of RPE cells intruded into the optic nerve sheath, indicating that the boundary between the retina and optic nerve may be displaced. Both PAX77 +/− and wild-type cells were involved in this ingression and in retinal folds, suggesting that neither effect was cell-autonomous. Cell-autonomous effects included failure of PAX77 +/− and wild-type cells to mix normally and overrepresentation of PAX77 +/− in the lens epithelium and RPE.
conclusions. The extent of PAX77 +/− eye abnormalities depended on PAX77 +/− genotype, genetic background, and stochastic variation. Chimera analysis identified two types of cell-autonomous effects of the PAX77 +/− genotype. Abnormal cell mixing between PAX77 +/− and wild-type cells suggests altered expression of cell surface adhesion molecules. Some phenotypic differences between PAX77 +/−↔wild-type and Pax6 +/−↔wild-type chimeras may reflect differences in the levels of PAX77 +/− and Pax6 +/− contributions to chimeric lenses.
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