Disruption of Mouse Corneal Epithelial Differentiation by Conditional Inactivation of<i>Pnn</i>

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 beta-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.