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Molecular and Cellular Biology, July 2000, p. 5248-5255, Vol. 20, No. 14
Department of Molecular and Cellular
Biology1 and Department of
Dermatology,2 Baylor College of Medicine,
Houston, Texas 77030
Received 7 February 2000/Returned for modification 6 April
2000/Accepted 13 April 2000
Keratin 6 (K6) expression in the epidermis has two components:
constitutive expression in the innermost layer of the outer root sheath
(ORS) of hair follicles and inducible expression in the interfollicular
epidermis in response to stressful stimuli such as wounding. Mice
express two K6 isoforms, MK6a and MK6b. To gain insight into the
functional significance of these isoforms, we generated MK6a-deficient
mice through mouse embryonic stem cell technology. Upon wounding, MK6a
was induced in the outer ORS and the interfollicular epidermis
including the basal cell layer of MK6a+/+ mice, whereas
MK6b induction in MK6a
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Copyright © 2000, American Society for Microbiology. All rights reserved.
Delayed Wound Healing in Keratin 6a Knockout
Mice
/
mice was restricted to the
suprabasal layers of the epidermis. After superficial wounding of the
epidermis by tape stripping, MK6a
/
mice showed a delay
in reepithelialization from the hair follicle. However, the healing of
full-thickness skin wounds was not impaired in MK6a
/
animals. Migration and proliferation of MK6a
/
keratinocytes were not impaired in vitro. Furthermore, the migrating and the proliferating keratinocytes of full-thickness wounds in MK6a
/
animals expressed neither MK6a nor MK6b. These
data indicate that MK6a does not play a major role in keratinocyte
proliferation or migration but point to a role in the activation of
follicular keratinocytes after wounding. This study represents the
first report of a keratin null mutation that results in a wound healing defect.
*
Corresponding author. Mailing address: Department of
Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4966. Fax: (713) 798-3800. E-mail: roopd{at}bcm.tmc.edu.
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