International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


J Jaubert

Cheng J, Segre

The epidermis is a multilayered tissue, with an inner basal layer of proliferating cells and suprabasal layers of progressively differentiating cells. Located at the interface between body and environment, one of its roles is to act as a barrier to protect against dehydratation. In mice, the epidermal barrier function starts to establish around embryonic day E16.5 and is fully established at day E17.5. KLF4 is a zinc-finger transcription factor of the Kruppel-like family, expressed in epithelial cells of different organs, mainly skin, lungs and gut. Knock-out mice for Klf4 gene, showed that this transcription factor is required for establishing the skin barrier function. To further characterize the exact role of KLF4 in this process we chose to study the effect of a gain of function of KLF4. We overexpressed KLF4 one stage earlier in development, i.e. in the basal layer of the epidermis instead of the suprabasal layers, using a conditional approach with the tetracycline system. We used a previously established driver line (bovin promoter of keratin 5 gene) and constructed a myc-tagged-KLF4 responder line. A dye penetration assay showed that double transgenic mice establish their barrier earlier than wild-type controls, starting as early as day E15.5. Histology and immunohistochemistry showed that the skin of double transgenic mice is normal but advanced, with E15.5 skin already expressing markers of fully mature skin. Our results underscore the crucial role of KLF4 in establishing the epidermal barrier function and suggest that this factor is not only necessary but sufficient in this process.

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