BCL-X EXPRESSION INFLUENCES KERATINOCYTE CELL-SURVIVAL BUT NOT TERMINAL DIFFERENTIATION

The epidermis is characterized by the continual turnover of its basic cellular unit, the keratinocyte. To determine whether genes known to r egulate apoptosis could affect keratinocyte biology, transgenic mice o verexpressing bcl-x(L) or bcl-x(S) under the control of the human kera tin 14 promoter were generated, The maturation process and cellularity of the stratified epidermis were not compromised in the transgenic mi ce, Transgene function was demonstrated by enhanced cell survival of b cl-x(L) transgenic versus wildtype primary keratinocyte cultures treat ed with etoposide, To test the response of these mice to genotoxic dam age, wild-type and transgenic mice were irradiated with UV light, The bcl-x(L) transgenic mice showed a dramatically increased resistance to irradiation, whereas the bcl-x(S) transgenic mice showed an increased sensitivity to irradiation, In contrast, neither transgene influenced the rate of wound repair, Interestingly, endogenous Bcl-x was rapidly induced in keratinocytes adjacent to the wound, Taken together, these findings demonstrate that although the terminal differentiative progr am is not altered by Bcl-x, acute stress responses within the skin can be influenced by regulators of apoptosis such as Bcl-x.