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J Biol Chem, Vol. 273, Issue 37, 23904-23911, September 11, 1998

Mouse Keratin 4 Is Necessary for Internal Epithelial Integrity

Seth L. NessDagger , Winfried EdelmannDagger , Timothy D. Jenkins, Wolfgang Liedtke**Dagger Dagger , Anil K. Rustgi§§, and Raju KucherlapatiDagger

From the Dagger  Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, the  Gastrointestinal Unit and the §§ Hematology-Oncology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, and the ** Department of Pathology/Division of Neuropathology, Albert Einstein College of Medicine, Bronx, New York 10461 and Dagger Dagger  Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10023

Keratins are intermediate filaments of epithelial cells. Mutations in keratin genes expressed in skin lead to human disorders, including epidermolysis bullosa simplex and epidermolytic hyperkeratosis. We examined the role of keratin 4 (K4) in maintaining the integrity of internal epithelial linings by using gene targeting to generate mice containing a null mutation in the epithelial K4 gene. Homozygous mice that do not express K4 develop a spectrum of phenotypes that affect several organs which express K4 including the esophagus, tongue, and cornea. The cellular phenotypes include basal hyperplasia, lack of maturation, hyperkeratosis, atypical nuclei, perinuclear clearing, and cell degeneration. These results are consistent with the notion that K4 is required for internal epithelial cell integrity. As mutations in K4 in humans lead to a disorder called white sponge nevus, the K4-deficient mice may serve as models for white sponge nevus and for understanding the role of K4 in cellular proliferation and differentiation.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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