Sites of Cre-recombinase activity in mouse lines targeting skeletal cells.

The Cre/Lox system is a powerful tool in the biologist's toolbox, allowing loss and gain-of-function studies, as well as lineage tracing, through gene recombination in a tissue-specific and inducible manner. Evidence indicates, however, that Cre transgenic lines have a far more nuanced and broader pattern of Cre activity than initially thought, exhibiting "off-target" activity in tissues/cells other than the ones they were originally designed to target. With the goal of facilitating the comparison and selection of optimal Cre lines to be used for the study of gene function, we have summarized in a single manuscript the major sites and timing of Cre activity of the main Cre lines available to target bone mesenchymal stem cells, chondrocytes, osteoblasts, osteocytes, tenocytes and osteoclasts, along with their reported sites of "off-target" Cre activity. We also discussed characteristics, advantage and limitations of these Cre lines for users to avoid common risks related to over- or misinterpretation based on the assumption of strict cell-type specificity or unaccounted effect of the Cre transgene or Cre inducers. This article is protected by copyright. All rights reserved.