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J Biol Chem, Vol. 273, Issue 37, 23904-23911, September 11, 1998
From the 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.
Mouse Keratin 4 Is Necessary for Internal Epithelial
Integrity
,,,
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
Howard Hughes Medical Institute, The
Rockefeller University, New York, New York 10023
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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