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© The Rockefeller University Press, 0021-9525/1998//1035 $5.00
The Journal of Cell Biology, Volume 142, Number 4, , 1998 1035-1051

Directed Expression of Keratin 16 to the Progenitor Basal Cells of Transgenic Mouse Skin Delays Skin Maturation

Department of Biological Chemistry and Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

We previously hypothesized that the type I keratin 16 (K16) plays a role in the process of keratinocyte activation that occurs in response to skin injury (Paladini, R.D., K. Takahashi, N.S. Bravo, and P.A. Coulombe. 1996. J. Cell Biol. 132:381–397). To further examine its properties in vivo, the human K16 cDNA was constitutively expressed in the progenitor basal layer of transgenic mouse skin using the K14 gene promoter. Mice that express approximately as much K16 protein as endogenous K14 display a dramatic postnatal phenotype that consists of skin that is hyperkeratotic, scaly, and essentially devoid of fur. Histologically, the epidermis is thickened because of hyperproliferation of transgenic basal cells, whereas the hair follicles are decreased in number, poorly developed, and hypoproliferative. Microscopically, the transgenic keratinocytes are hypertrophic and feature an altered keratin filament network and decreased cell–cell adhesion. The phenotype normalizes at 5 wk after birth. In contrast, control mice expressing a K16-K14 chimeric protein to comparable levels are normal. The character and temporal evolution of the phenotype in the K16 transgenic mice are reminiscent of the activated EGF receptor– mediated signaling pathway in skin. In fact, tyrosine phosphorylation of the EGF receptor is increased in the newborn skin of K16 transgenic mice. We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain.

Key Words: skin • keratin • adhesion • wound repair • transgenic mouse

Our thanks to Ms. S. Brust and Ms. A. Chen (Johns Hopkins University, Transgenic Core Facility) for the production of transgenic mice. Special thanks are due to Dr. E. Fuchs and Dr. T. Tanaka for providing the K14 expression cassette. We also thank Dr. M. Takaechi (E-cadherin), Dr. R. Hynes (3 and β1 integrins), Dr. F. Giancotti (6 and β4 integrins), Dr. D. Paul (connexin 26), Dr. B. Dale (filaggrin), Dr. I. Leigh (keratins 14 and 16), Dr. K. Green (desmoplakin), and Dr. E. Fuchs (keratin 5) for providing antibodies. Dr. L. Hansen provided valuable help for the EGFR Western experiments. Thanks also to Dr. J. Porter and Dr. K. McGowan for their help.

P.A. Coulombe is the recipient of a Junior Faculty Research Award from the American Cancer Society. This work was supported by National Institutes of Health grant AR44232.

Address all correspondence to Pierre A. Coulombe, Ph.D., Dept. of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205. Tel.: (410) 614-0510. Fax: (410) 955-5759. E-mail: coulombe{at}jhu.edu

1. Abbreviation used in this paper: EGFR, EGF receptor.

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