Ligand-activated Flpe for temporally regulated gene modifications

Nina L. Hunter, Rajeshwar B. Awatramani, Francis W. Farley, Susan M. Dymecki*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The selectivity by which site-specific recombinase-mediated genetic changes can be targeted to specific cells in the mouse has been limited by the fact that many genes used as recombinase "drivers" are expressed either in cell populations that change over time or constitutively in a given cell population for an extended time period, for example, in a germinal zone that gives rise successively to different lineages. These scenarios limit the selective dimension of conditional gene modification experiments as they preclude studying the later-generated lineages either because of earlier phenotypes (in the case of conditional mutagenesis experiments) or because the early and permanent activation of a reporter in a germinal zone results in all descendant lineages being marked (in the case of fate-mapping experiments). To circumvent this limitation, inducible forms of Cre recombinase have been developed, enabling the induction of genetic changes in late embryonic or adult cells accessible only through late aspects of a dynamic driver gene expression profile. To increase the number of tools available for engineering genetic changes in selective cell populations, we have generated a ligand-regulated form of Flpe using the recombinase-steroid receptor fusion approach. In two prototypical scenarios, we show that the fused gene product, FlpeER T2, is competent to mediate DNA recombination in vivo and responds specifically to the inducer tamoxifen in a dose-dependent manner without detectable background activity.

Original languageEnglish (US)
Pages (from-to)99-109
Number of pages11
JournalGenesis
Volume41
Issue number3
DOIs
StatePublished - Mar 1 2005

Keywords

  • Flpe
  • Induction
  • Recombinase
  • Tamoxifen

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Ligand-activated Flpe for temporally regulated gene modifications'. Together they form a unique fingerprint.

  • Cite this