Effects of elevated Pax6 expression and genetic background on mouse eye development

Simon A Chanas, J Martin Collinson, Thaya Ramaesh, Natalie Dora, Dirk A Kleinjan, Robert E Hill, John D West

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)4045-4059
Number of pages5
JournalInvestigative Ophthalmology & Visual Science
Issue number9
Early online date22 Apr 2009
Publication statusPublished - Sept 2009


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