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Cre-recombinase mediated conditional deletion of  Lox-P  site flanked (" floxed ") genes is widely used for functional gene annotation in mice. Many different  Cre -transgenic mouse lines have been developed for cell-type specific gene disruption. But often, the precise tissue-patterns of  Cre  activity remain incompletely characterized. Two widely used transgenes for conditional gene recombination in hematopoietic cells are  Vav-iCre  driven from the  murine Vav1  promotor, and  hCD2-iCre  driven from the  human CD2  promotor.  Vav-iCre  expresses active Cre in fetal and adult hematopoietic stem cells and all descendants,  hCD2-iCre  in immature and mature B and T lymphocytes. To better characterize which hematopoietic cells contain  hCD2-iCre  activity, we compared EYFP fluorescence in  hCD2-iCre +/-  R26-stop-EYFP +/-   and  Vav-iCre +/-  R26-stop-EYFP +/-  mice.  R26-stop-EYFP  ubiquitously encodes  EYFP  preceded by a  floxed stop  cassette. By removing it, Cre activity induces measurable EYFP expression. Our results confirm the known activity patterns for both  Cre  transgenes and unveil additional  hCD2-iCre  mediated reporter gene recombination in common lymphoid progenitors, in natural killer cells and their progenitors, and in plasmacytoid and conventional dendritic cells. This supports previously proposed common lymphoid origins for natural killer cells and subsets of dendritic cells, and indicates the need to consider pleiotropic effects when studying  hCD2-iCre  mediated conditional knockout mice.  Vav-iCre +/-  R26-stop-EYFP +/-  mice did not show the non-hematopoietic recombination in vascular endothelial cells seen in other  Vav-Cre  mouse lines, but displayed an unexpected  Vav-iCre  mediated recombination in a bone cell subset lacking hematopoietic markers. This pinpoints the need to consider stromal cell contributions to phenotypes of  Vav-iCre  mediated conditional knockout mice. Altogether, our data provide the first detailed assessment of  hCD2-iCre  and  Vav-iCre  mediated deletion of  floxed  genes during lymphocyte development from hematopoietic stem cells and open up novel applications for either  Cre-transgenic  mouse line.

hCD2-iCre and Vav-iCre Mediated Gene Recombination Patterns in Murine Hematopoietic Cells