Trangenic misexpression of the differentiation-specific desmocollin isoform 1 in basal keratinocytes

Keratinocytes undergoing terminal differentiation are characterized by well -defined changes in protein expression, which contribute towards the transf ormation of cytoarchitecture and epithelial morphology, Characteristic patt erns of desmosomal cadherins are tightly regulated and distinct isoforms ar e expressed during development and differentiation of epithelial tissues, D esmocollin-1 is strictly confined to suprabasal layers of epidermis, but it is absent in mitotically active, basal keratinocytes. This raises the ques tion of whether basal desmocollin-1 could alter desmosomal functions and co mpromise keratinocyte proliferation, stratification, or early differentiati on in skin. In this study, we misexpressed human desmocollin-1 in mouse epi dermis, under control of the keratin-14 promoter. Transgenic animals were g enerated, which showed a specific expression of transgenic human desmocolli n-1 in epidermal basal cells. High level transgenic expression, which was e qual to or greater than endogenous protein levels, was observed in mice wit h multiple copy integration of the transgene. A punctate distribution of de smocollin-1 was demonstrated at the cell membrane by indirect immunofluores cence. Transgenic human desmocollin-1 colocalized with endogenous desmosoma l marker proteins, indicating efficient incorporation into desmosomes. Tran sgenic mice did not display any obvious abnormalities, either in the histol ogy of skin and hair follicles, or in the ultrastructure of desmosomes. The se observations suggest that desmocollin-1 can function as a desmosomal cad herin both in basal and suprabasal cells. We propose that the differentiati on-specific desmocollin isoforms desmocollin-1 and desmocollin-3 are functi onally equivalent in basal epidermal cells and suggest that their changing expression patterns are markers, but not regulators, of the initial steps i n keratinocyte differentiation.