Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus

Sci Rep. 2020 Jan 14;10(1):207. doi: 10.1038/s41598-019-57052-z.


Using an efficient gene targeting approach, we developed a novel mouse line that expresses the tetracycline-controlled transactivator (tTA) from the constitutively active Eef1a1 locus in a Cre recombinase-inducible manner. The temporally and spatially controlled expression of the EF1-LSL-tTA knockin and activation of tTA-driven responder transgenes was tested using four transgenic lines that express Cre under tissue-specific promoters of the pancreas, mammary gland and other secretory tissues, as well as an interferon-inducible promoter. In all models, the endogenous Eef1a1 promoter facilitated a cell-type-specific activation of target genes at high levels without exogenous enhancer elements. The applicability of the EF1-LSL-tTA strain for biological experiments was tested in two studies related to mammary gland development and tumorigenesis. First, we validated the crucial role of active STAT5 as a survival factor for functionally differentiated epithelial cells by expressing a hyperactive STAT5 mutant in the mammary gland during postlactational remodeling. In a second experiment, we assessed the ability of the EF1-tTA to initiate tumor formation through upregulation of mutant KRAS. The collective results show that the EF1-LSL-tTA knockin line is a versatile genetic tool that can be applied to constitutively express transgenes in specific cell types to examine their biological functions at defined developmental stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Female
  • Gene Expression Regulation / drug effects*
  • Genes, Reporter
  • Integrases / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Peptide Elongation Factor 1 / genetics
  • Peptide Elongation Factor 1 / metabolism*
  • Promoter Regions, Genetic
  • Tetracycline / pharmacology*
  • Tissue Distribution
  • Trans-Activators
  • Transgenes / physiology*


  • Anti-Bacterial Agents
  • Eef1a1 protein, mouse
  • Peptide Elongation Factor 1
  • Trans-Activators
  • Cre recombinase
  • Integrases
  • Tetracycline