Mammalian Genome

, Volume 11, Issue 3, pp 196–205

Conditional mutagenesis in mice with heat shock promoter-driven cre transgenes

  • Paula  Dietrich
  • Ioannis  Dragatsis
  • Shouhong  Xuan
  • Scott  Zeitlin
  • Argiris  Efstratiadis
Article

DOI: 10.1007/s003350010037

Cite this article as:
Dietrich, P., Dragatsis, I., Xuan, S. et al. Mammalian Genome (2000) 11: 196. doi:10.1007/s003350010037

Abstract.

To explore the potential of a simple and rapid approach for ubiquitous conditional gene disruption, we have generated Cre-producer mouse transgenic lines (Hs-cre1, 6 and 7) expressing a recombinase transgene (cre) from a heat shock gene promoter and tested their performance in Cre-mediated excision of target DNA in crosses with Cre-responder strains carrying loxP-modified alleles of the genes encoding the Huntington's disease gene homolog (Hdh), the epidermal growth factor receptor (Egfr), and the type 1 insulin-like growth factor receptor (Igf1r). Analyses of progeny possessing various transgene/reporter combinations showed that cre expression can occur without heat shock in early embryos, but this constitutive transcription is stochastic and transgene dependent. Thus, Hs-cre1 behaves predominantly as a ``deleter'' strain, since the majority of progeny (∼70–85%) exhibit complete recombination, regardless of reporter locus. Lines Hs-cre6 and Hs-cre7, however, function successfully as ``mosaicking'' strains because, in addition to two extreme classes of progeny with 0% or 100% recombination, they generate an intermediate class of mosaics exhibiting various degrees of partial DNA excision. Notably, the frequency of offspring in each class varies between reporters, but mosaic embryos are consistently obtained in adequate numbers (∼30–60%). The Hs-cre6 transgene is also inducible and can be used to introduce mosaicism into adult tissues at preselected developmental times by heat shock treatment of mice with 0% recombination in tail DNA. By bypassing the lethality resulting from some gene knockouts, mosaic embryos and mice make particular mutational analyses possible and are also very useful for the identification of cell lineage-specific gene functions.

Copyright information

© Springer-Verlag New York Inc. 2000

Authors and Affiliations

  • Paula  Dietrich
    • 1
  • Ioannis  Dragatsis
    • 1
  • Shouhong  Xuan
    • 1
  • Scott  Zeitlin
    • 2
  • Argiris  Efstratiadis
    • 1
  1. 1.Department of Genetics and Development, Columbia University, Russ Berrie Medical Sciences Pavilion, 1150 St. Nicholas Ave., New York, New York 10032, USAUS
  2. 2.Department of Pathology, Columbia University, 1150 St. Nicholas Ave., New York, New York 10032, USAUS