Mouse keratin 4 is necessary for internal epithelial integrity

Seth L. Ness, Winfried Edelmann, Timothy D. Jenkins, Wolfgang Liedtke, Anil K. Rustgi, Raju Kucherlapati

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)23904-23911
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number37
DOIs
StatePublished - Sep 11 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ness, S. L., Edelmann, W., Jenkins, T. D., Liedtke, W., Rustgi, A. K., & Kucherlapati, R. (1998). Mouse keratin 4 is necessary for internal epithelial integrity. Journal of Biological Chemistry, 273(37), 23904-23911. https://doi.org/10.1074/jbc.273.37.23904