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.