Temporal, spatial, and cell type-specific control of Cre-mediated DNA recombination in transgenic mice

Nat Biotechnol. 1999 Nov;17(11):1091-6. doi: 10.1038/15073.


We have developed a universal system for temporal, spatial, and cell type-specific control of gene expression in mice that (1) integrates the advantages of tetracycline-controlled gene expression and Cre-recombinase-loxP site-mediated gene inactivation, and (2) simplifies schemes of animal crosses by combination of two control elements in a single transgene. Two transgenic strains were generated in which the cell type-specific control was provided by either the retinoblastoma gene promoter or the whey acidic protein promoter. Both promoters drive the expression of the reverse tetracycline-controlled transactivator (rtTA). Placed in cis configuration to the rtTA transcription unit, the rtTA-inducible promoter directs expression of Cre recombinase. In both strains crossed with cActXstopXLacZ reporter mice, which have a loxP-stop of transcription/translation-loxP-LacZ cassette driven by chicken beta-actin promoter, Cre-loxP-mediated DNA recombination leading to LacZ expression was accurately regulated in a temporal, spatial, and cell type-specific manner. This approach can be applied to establishment of analogous mouse strains with virtually any promoter as systems to control gene regulation in a variety of cell types.

Publication types

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

MeSH terms

  • Animals
  • Doxycycline / pharmacology
  • Female
  • Gene Deletion
  • Gene Expression Regulation*
  • Integrases / metabolism*
  • Mammary Glands, Animal / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Recombination, Genetic*
  • Tetracycline / pharmacology
  • Trans-Activators
  • Transgenes
  • Viral Proteins*


  • Trans-Activators
  • Viral Proteins
  • Cre recombinase
  • Integrases
  • Tetracycline
  • Doxycycline