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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.

SUBMITTER: Gregoire D 

PROVIDER: S-EPMC2567143 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Grégoire Damien D   Kmita Marie M  

Proceedings of the National Academy of Sciences of the United States of America 20080911 38


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-media  ...[more]

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