Delayed wound healing in keratin 6a knockout mice

Keratin 6 (K6) expression in the epidermis has two components: constitutive expression in the innermost layer of the outer root sheath (ORS) of hair f ollicles and inducible expression in the interfollicular epidermis in respo nse to stressful stimuli such as wounding. Mice express two K6 isoforms, MK 6a and MK6b. To gain insight into the functional significance of these isof orms, we generated MK6a-deficient mice through mouse embryonic stem cell te chnology. Upon wounding, MK6a was induced in the outer ORS and the interfol licular epidermis including the basal cell layer of MK6a(+/+) mice, whereas MK6b induction in MK6a(-/-) mice was restricted to the suprabasal layers o f the epidermis. After superficial mounding of the epidermis by tape stripp ing, MK6a(-/-) mice showed a delay in reepithelialization from the hair fol licle. However, the healing of full-thickness skin wounds was not impaired in MK6a(-/-) animals. Migration and proliferation of MK6a(-/-) keratinocyte s were not impaired in vitro. Furthermore, the migrating and the proliferat ing keratinocytes of full-thickness wounds in MK6a(-/-) animals expressed n either MK6a nor MK6b. These data indicate that MK6a does not play a major r ole in keratinocyte proliferation or migration but point to a role in the a ctivation of follicular keratinocytes after wounding. This study represents the first report of a keratin null mutation that results in a wound healin g defect.