Functional importance in epidermal development and homeostasis has been shown for numerous transcription factors, yet little is known about their possible involvement in blistering skin diseases. Ovol1 and Ovol2 transcription factors play important roles in epidermal morphogenesis: Ovol1 ablation expands the suprabasal spinous layers, whereas simultaneous loss of Ovol1 and Ovol2 results in defective cell adhesion and terminal differentiation (Lee et al., 2014; Nair et al., 2006). In these previous studies, we generated tetracycline responsive element-Ovol2/K5-tTA bitransgenic (BT) mice, which robustly overexpress Ovol2 in the developing basal layer and produce a thinner embryonic epidermis (Lee et al., 2014). However, how the accumulated developmental defects manifest at birth was not characterized. In the experiments (approved by UC Irvine) below, we obtained evidence that Ovol2 overexpression during embryogenesis causes skin blistering at birth.