Development of a single-cassette system for spatiotemporal gene regulation in mice

Biochem Biophys Res Commun. 2005 Dec 16;338(2):1083-8. doi: 10.1016/j.bbrc.2005.10.054. Epub 2005 Oct 21.


The tetracycline-regulated gene expression system has been widely used in mice to turn a transgene on and off in a target organ, but with only limited success. We developed an advanced system in which a Tet-off regulation unit was integrated into the ROSA26 locus and became active after Cre-mediated excision of the neo(r) gene. We examined the utility of this system through regulable expression of the homeodomain transcription factor pdx-1 and enhanced green fluorescent protein. The resulting mice showed strict tetracycline-regulable gene expression in all the organs where the neo(r) gene had been removed. When combined with organ-specific Cre recombinase transgenic mice, our system allows us to manipulate the gene expression in an organ-specific and temporal manner. This Tet-off system should serve as an efficient tool to analyze the roles of genes in complex biological systems, such as embryogenesis, metabolism, immune system, etc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Gene Silencing
  • Genetic Engineering / methods*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • Mice, Transgenic / metabolism*
  • Recombinant Proteins / metabolism
  • Tetracycline / pharmacology
  • Tissue Distribution
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / physiology


  • Homeodomain Proteins
  • Recombinant Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Tetracycline