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Originally published In Press as doi:10.1074/jbc.M205143200 on July 15, 2002

J. Biol. Chem., Vol. 277, Issue 38, 35371-35377, September 20, 2002
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Severe Abnormalities in the Oral Mucosa Induced by Suprabasal Expression of Epidermal Keratin K10 in Transgenic Mice*

Mirentxu SantosDagger , Ana Bravo§, Ceferino López§, Jesús M. ParamioDagger , and José L. JorcanoDagger

From the Dagger  Project on Cell and Molecular Biology and Gene Therapy, CIEMAT Av. Complutense 22, E-28040 Madrid, Spain and the § Department of Animal Pathology, Veterinary School, University of Santiago de Compostela, 27002 Lugo, Spain

Previous studies have demonstrated that keratin K10 plays an important role in mediating cell signaling processes, since the ectopic expression of this keratin induces cell cycle arrest in proliferating cells in vitro and in vivo. However, apart from its well known function of providing epithelial cells with resilience to mechanical trauma, little is known about its possible roles in nondividing cells. To investigate what these might be, transgenic mice were generated in which the expression of K10 was driven by bovine K6beta gene control elements (bK6beta hK10). The transgenic mice displayed severe abnormalities in the tongue and palate but not in other K6-expressing cells such as those of the esophagus, nails, and hair follicles. The lesions in the tongue and palate included the cytolysis of epithelial suprabasal cells associated with an acute inflammatory response and lymphocyte infiltration. The alterations in the oral mucosa caused the death of transgenic pups soon after birth, probably because suckling was impaired. These anomalies, together with others found in the teeth, are reminiscent of the lesions observed in some patients with pachyonychia congenita, an inherited epithelial fragility associated with mutations in keratins K6 and K16. Although no epithelial fragility was observed in the bK6beta hK10 oral epithelia of the experimental mice, necrotic processes were seen. Collectively, these data show that the carefully regulated tissue- and differentiation-specific patterns displayed by the keratin genes have dramatic consequences on the biological behavior of epithelial cells and that changes in the specific composition of the keratin intermediate filament cytoskeleton can affect their physiology, in particular those of the oral mucosa.


* This work was supported in part by Spanish MCYT Grant PB94-1230 and CAM Grant 08.1/0054/2001.1.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 34-91-3466438; Fax: 34-91346484; E-mail: jesusm.paramio@ciemat.es.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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