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Fig. 2. Histological and ultrastructural abnormalities in ß4 null skin. (A) Inflamed ear of a 4-month-old mouse of the genotype ß4^flox/flox; K14-Cre. (B) Expression pattern of the Cre-recombinase in the skin of a 15.5-day-old embryo of the genotype ROSA26-pGK-neo-pA-LacZ-pA; K14-Cre, as assessed by X-gal staining. The non-stochastic expression of the Cre-recombinase at that stage has been described previously (Jonkers et al., 2001). The efficiency of K14-Cre-mediated recombination towards the ß4^flox alleles is such that expression of the ß4 gene remained largely mosaic even after birth. (C) Cryosection of skin from a newborn ß4^flox/flox; K14-Cre mouse stained with hematoxylin and eosin showing the presence of a small blister. The double-headed arrow denotes separation of the epidermis from the dermis. (D) Electron microscopy of the skin of a ß4^flox/flox; K14-Cre mouse shows a blistered area (double-headed arrow) infiltrated by leukocytes (L). The keratinocytes that had detached from the dermis lacked discernible HDs. (E) Immuno-electron microscopy of ß4^flox/flox; K14-Cre skin with primary antibodies against ß4 demonstrates gold particles associated with HDs at the base of a non-recombined keratinocyte. The neighboring cell to the right has probably degenerated as a result of an inflammatory reaction. The dotted line demarcates the boundary of the cell. BM, basement membrane; Nu, nucleus; HD, hemidesmosome; D, desmosome; L, leukocyte.

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