Fig. 4. Skin phenotype of adult Dsc3^fl/fl/K14-Cre mice. (A) A 160-day-old mutant mouse showing severe skin lesions, including a partial loss of the epidermis and hair follicles. (B,C) Histological analysis of the mouse shown in A. (B) Massive inflammation, scarring and re-epithelialization in an area where the epidermis was completely lost. A thin tongue of keratinocytes is migrating underneath the scab in an attempt to re-epithelialize the wound bed (the tongue is marked by a green double-headed arrow). The cells of this epithelial tongue undergo acantholysis (loss of cell–cell adhesion leading to blistering), a phenotype that might be the cause of wound healing defect and persistent skin blistering in older mice. Arrows indicate basal keratinocytes that have lost their adhesion to suprabasal cells, but that are still attached to the basement membrane. Owing to the severity of this phenotype, we now do not maintain these mice beyond 3 months of age. Star indicates blister cavity. (C) Hyperplastic area of mutant epidermis. (D) Age-matched normal skin of a wild-type mouse. The epidermis is only approximately two cell layers thick. (E) Immunofluorescence staining of hyperplastic mutant epidermis with K14 (red) and Ki67 (green) antibodies. The number of proliferating Ki67-positive nuclei (arrows) is dramatically increased compared with the wild-type control shown in F. (F) Age-matched wild-type epidermis stained with K14 (red) and Ki67 (green). Only a few keratinocytes in the interfollicular epidermis are Ki67 positive (arrows). Bars, 100 µm.