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Molecular and Cellular Biology, July 2000, p. 5248-5255, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Delayed Wound Healing in Keratin 6a Knockout Mice

Sonja M. Wojcik,1 Donnie S. Bundman,1 and Dennis R. Roop1,2,*

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-/- 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.

Molecular and Cellular Biology, July 2000, p. 5248-5255, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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