Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease

Robert Vassar, Pierre A. Coulombe, Linda Degenstein, Kathryn Albers, Elaine Fuchs

Research output: Contribution to journalArticle

Abstract

To explore the relationship between keratin gene mutations and genetic disease, we made transgenic mice expressing a mutant keratin in the basal layer of their stratified squamous epithelia. These mice exhibited abnormalities in epidermal architecture and often died prematurely. Blistering occurred easily, and basal cell cytolysis was evident at the light and electron microscopy levels. Keratin filament formation was markedly altered, with keratin aggregates in basal cells. In contrast, terminally differentiating cells made keratin filaments and formed a stratum corneum. Recovery of outer layer cells was attributed to down-regulation of mutant keratin expression and concomittant induction of differentiation-specific keratins as cells terminally differentiate, and the fact that these cells arose from basal cells developing at a time when keratin expression was relatively low. Collectively, the pathobiology and biochemistry of the transgenic mice and their cultured keratinocytes bore a resemblance to a group of genetic disorders known as epidermolysis bullosa simplex.

Original languageEnglish (US)
Pages (from-to)365-380
Number of pages16
JournalCell
Volume64
Issue number2
DOIs
StatePublished - Jan 25 1991
Externally publishedYes

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Genetic Skin Diseases
Medical Genetics
Keratins
Transgenic Mice
Skin
Inborn Genetic Diseases
Cells
Epidermolysis Bullosa Simplex
Biochemistry
Keratinocytes
Cornea
Electron microscopy
Optical microscopy
Electron Microscopy
Down-Regulation
Epithelium
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease. / Vassar, Robert; Coulombe, Pierre A.; Degenstein, Linda; Albers, Kathryn; Fuchs, Elaine.

In: Cell, Vol. 64, No. 2, 25.01.1991, p. 365-380.

Research output: Contribution to journalArticle

Vassar, Robert ; Coulombe, Pierre A. ; Degenstein, Linda ; Albers, Kathryn ; Fuchs, Elaine. / Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease. In: Cell. 1991 ; Vol. 64, No. 2. pp. 365-380.
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