title: Recombination between inverted loxP sites is cytotoxic for proliferating cells and provides a simple tool for conditional cell ablation.
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.
authors.affiliation: Laboratory of Genetics and Development, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, H2W1R7, Université de Montréal, Montréal Québec, Canada.
authors.forename: Damien
authors.initials: D
authors.lastname: Grégoire
authors.forename: Marie
authors.initials: M
authors.lastname: Kmita
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001287:Attachment Sites, Microbiological / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002872:Chromosome Deletion; D004622:Embryo, Mammalian / Q000166:cytology; D019426:Integrases / Q000378:metabolism*; D051379:Mice; D009006:Monosomy / Q000235:genetics*; D009928:Organ Specificity; D011995:Recombination, Genetic
chemical_list: C045073:Cre recombinase; D019426:Integrases
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