Disruption of Mouse Corneal Epithelial Differentiation by Conditional Inactivation ofPnn

Abstract

Purpose.: To investigate the specific role of Pinin (Pnn) in the development of anterior eye segment in mice. Methods.: Conditional inactivation of Pnn in the developing surface eye ectoderm and lens was achieved by creating mice carrying a Pnn null and a floxed Pnn allele as well as a Pax6-Cre-GFP (Le-Cre) transgene. The resultant Pnn conditional knockout mice were examined by histologic and immunohistologic approaches. Results.: Pax6-Cre–mediated deletion of Pnn resulted in severe malformation of lens placode-derived tissues including cornea and lens. Pnn mutant corneal epithelium displayed the loss of corneal epithelial identity and appeared epidermis-like, downregulating corneal keratins (K12) and ectopically expressing epidermal keratins (K10 and K14). This squamous metaplasia of Pnn mutant corneal epithelium closely correlated with significantly elevated β-catenin activity and Tcf4 level. In addition, Pnn inactivation also led to misregulated level of p68 RNA helicase in mutant corneal epithelium. Conclusions.: These data indicate that Pnn plays an essential role in modulating and/or orchestrating the activities of major developmental factors of anterior eye segments.