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

Cell. 1991 Jan 25;64(2):365-80. doi: 10.1016/0092-8674(91)90645-f.


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 evidence 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 concomitant 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Epithelium / pathology
  • Humans
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / isolation & purification
  • Keratins / analysis
  • Keratins / genetics*
  • Mice
  • Mice, Transgenic
  • Mutation*
  • Phenotype
  • Skin / pathology*
  • Skin / ultrastructure
  • Skin Diseases / genetics*
  • Skin Diseases / pathology


  • Intermediate Filament Proteins
  • Keratins