Ets1 in Squamous Neoplasia Figure 2. Ets1 expression results in dramatic alterations to skin homeostasis. (A) Time course of transgene induction. Ets1 expression is suppressed prenatally and postnatally by feeding the mothers a Dox-containing diet. After weaning at the age of 3 weeks, the Ets1 transgene is induced by switching the mice to a diet lacking Dox. The phenotype can be observed within 3–6 weeks after diet change. (B–D) Gross phenotype of several sets of adult WT and BT mice. Arrowheads point to sores, ulcers and crusting on the skin and paws of BT mice. Note that BT mice are substantially thinner than their wild type littermates. doi:10.1371/journal.pone.0004179.g002 associated with particular differentiated layers of the epidermis. As shown in Figure 4, keratinocytes in the skin of BT mice demonstrated significant alterations in the expression of these markers. In particular, expression of cytokeratins typically localized to the basal layer (K5 and K14) was expanded such that most of the cells in the epidermis stained positive for these proteins (Figure 4A and data not shown). In addition, most suprabasal cells in the epidermis of BT mice expressed K10, a cytokeratin normally restricted to the spinous layer (Figure 4B). In contrast, the expression of markers such as loricrin, filaggrin and involucrin, which are normally restricted to the granular layer of the epidermis, was decreased (Figure 4C and data not shown). PLoS ONE | www.plosone.org 4 January 2009 | Volume 4 | Issue 1 | e4179