Recombination between inverted loxP sites is cytotoxic for proliferating cells and provides a simple tool for conditional cell ablation

Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14492-6. doi: 10.1073/pnas.0807484105. Epub 2008 Sep 11.

Abstract

The loxP/Cre recombination system is a widely used tool for mouse functional genomics, in particular for in vivo conditional mutagenesis. Depending on the relative orientation and position of loxP sites, Cre-mediated recombination can result in a variety of targeted genomic rearrangements. It was previously reported that loss of the loxP-carrying chromosome can occur when loxP sites are arranged in inverse orientation. By using a chromosome 2 carrying inverted loxP sites, we found that Cre-mediated recombination not only causes chromosomal loss but also triggers apoptosis. We show that targeted recombination between inverted loxP sites (TRIP) triggers cell death specifically in proliferating Cre-expressing cells, and we provide evidence that TRIP is an efficient tool to ablate proliferating cells within genetically defined cell populations. Furthermore, the procedure requires only a simple, one-step intercross but neither the use of toxins nor the additional step of prodrug injection. With the large repertoire of tissue-specific or inducible Cre-expressing transgenes available, TRIP-mediated cell ablation is valuable to investigate the function of a large variety of cell populations in the context of a whole organism, which includes mechanisms underlying organ development and tissue homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Attachment Sites, Microbiological / genetics*
  • Cell Proliferation
  • Cell Survival / genetics
  • Chromosome Deletion
  • Embryo, Mammalian / cytology
  • Integrases / metabolism*
  • Mice
  • Monosomy / genetics*
  • Organ Specificity
  • Recombination, Genetic*

Substances

  • Cre recombinase
  • Integrases