Targeted somatic mutagenesis in mouse epidermis

Horm Res. 2000;54(5-6):296-300. doi: 10.1159/000053275.

Abstract

Gene targeting in the mouse is a powerful tool to study mammalian gene function. The possibility to efficiently introduce somatic mutations in a given gene, at a chosen time and/or in a given cell type will further improve such studies, and will facilitate the generation of animal models for human diseases. To create targeted somatic mutations in the epidermis, we established transgenic mice expressing the bacteriophage P1 Cre recombinase or the tamoxifen-dependent Cre-ER(T2) recombinase under the control of the human keratin 14 (K14) promoter. We show that LoxP flanked (floxed) DNA segments were efficiently excised in epidermal keratinocytes of K14-Cre transgenic mice. Furthermore, Tamoxifen administration to adult K14-Cre-ER(T2) mice efficiently induced recombination in the basal keratinocytes, whereas no background recombination was detected in the absence of ligand treatment. These two transgenic lines should be very useful to analyse the functional role of a number of genes expressed in keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriophage P1 / enzymology
  • Epidermal Cells
  • Epidermis / drug effects
  • Epidermis / physiology*
  • Estrogen Antagonists / pharmacology
  • Gene Targeting*
  • Humans
  • Integrases / genetics
  • Keratin-14
  • Keratinocytes / drug effects
  • Keratinocytes / physiology
  • Keratins / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Site-Directed*
  • Mutation
  • Receptors, Estrogen / genetics
  • Recombination, Genetic
  • Tamoxifen / pharmacology
  • Viral Proteins / genetics

Substances

  • Estrogen Antagonists
  • KRT14 protein, human
  • Keratin-14
  • Krt14 protein, mouse
  • Receptors, Estrogen
  • Viral Proteins
  • Tamoxifen
  • Keratins
  • Cre recombinase
  • Integrases