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Minh-Thanh T. Nguyen, Chia-yang Liu, Ruth Ashery-Padan, Winston W. Kao; Investigation Of Pax6 Function In Mouse Ocular Surface Mesenchyme Using A Tissue Specific Mouse Model, Wnt1cre+/Pax6flox/RosamTmG. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1925.
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To determine the role of Pax6 in the periocular mesenchymal cells, which contribute to corneal stromal, endothelial, trabecular meshwork, and iris and ciliary body stromal development.
We crossed Wnt1Cre with Pax6flox/flox and ROSAmTmG/mTmG transgenic mice to ablate Pax6 in periocular mesenchymal cells in triple transgenic animals, Wnt1cre/Pax6flox/+/ROSAmTmG/+ and Wnt1cre/Pax6flox/flox/ROSAmTmG/+. Pax6 was conditionally deleted in Wnt1Cre+ cells. The effect of heterozygous (Pax6flox/+) or homozygous (Pax6flox/flox) Pax6 deletion in the Wnt1Cre+ cells was examined by stereomicroscope and by immunohistochemistry. All reported research was conducted in compliance with the ARVO statement for the Use of Animals in Ophthalmic and Vision Research.
About 50% of Wnt1cre+/Pax6flox/+/ROSAmTmG mice developed corneal haze and growth of blood and lymphatic vessels from the limbus into the central cornea by 12 weeks. Wnt1cre+/Pax6flox/flox/ROSAmTmG mice died from hydrocephaly starting around 4 to 6 weeks post-natal. The dome-shaped head is already recognizable at day 12 post-natal. H&E staining of Wnt1cre+/Pax6flox/flox/ROSAmTmG 4 weeks-old mice indicated that the iridocorneal angle, the iris and ciliary body (CB) stroma, the corneal stroma and the endothelial layers are not affected. Immunofluorescent staining with anti-LYVE1 antibody showed that the lymphatic vessels developed beyond the boundary between limbus and peripheral cornea.
The Wnt1cre+/Pax6flox/ROSAmTmG transgenic line allows us to study the functional role of Pax6 in the periocular mesenchymal cells. The ablation of Pax6 in Wnt1Cre+ cells do not lead to iris and CB stromal, corneal stromal, nor corneal endothelial defects. However, it appeared to affect corneal lymphangiogenesis/angiogenesis.
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