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Publication : Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation.

First Author  Liu J Year  2013
Journal  Genesis Volume  51
Issue  6 Pages  436-42
PubMed ID  23441020 Mgi Jnum  J:204870
Mgi Id  MGI:5543575 Doi  10.1002/dvg.22384
Citation  Liu J, et al. (2013) Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation. Genesis 51(6):436-42
abstractText  Cre/LoxP-mediated recombination allows for conditional gene activation or inactivation. When combined with an independent lineage-tracing reporter allele, this technique traces the lineage of presumptive genetically modified Cre-expressing cells. Several studies have suggested that floxed alleles have differential sensitivities to Cre-mediated recombination, which raises concerns regarding utilization of Cre-reporters to monitor recombination of other floxed loci of interest. Here, we directly investigate the recombination correlation, at cellular resolution, between several floxed alleles induced by Cre-expressing mouse lines. The recombination correlation between different reporter alleles varied greatly in otherwise genetically identical cell types. The chromosomal location of floxed alleles, distance between LoxP sites, sequences flanking the LoxP sites, and the level of Cre activity per cell all likely contribute to observed variations in recombination correlation. These findings directly demonstrate that, due to non-parallel recombination events, commonly available Cre reporter mice cannot be reliably utilized, in all cases, to trace cells that have DNA recombination in independent-target floxed alleles, and that careful validation of recombination correlations are required for proper interpretation of studies designed to trace the lineage of genetically modified populations, especially in mosaic situations.
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