F. Henkler et al., Trangenic misexpression of the differentiation-specific desmocollin isoform 1 in basal keratinocytes, J INVES DER, 116(1), 2001, pp. 144-149
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.