Variegate expression of Cre recombinase in hematopoietic cells in CD11c-cre transgenic mice

In this study, we performed an in-depth analysis of Cre expression in the widely used CD11c-Cre transgenic mice generated by the group of Boris Reizis. In contrast to previous observation, using the highly sensitive Rosa-26-floxed-tdTomato reporter mouse line, we show variegated expression of Cre in multiple hematopoietic linage cells starting in hematopoietic stem cells. We found that in the CD11c-Cre driver mice: (1) Cre is expressed in cDC linage cells and pDC starting from the myeloid dendritic cell precursor, as expected ; (2) Cre is expressed in a substantial fraction of hematopoietic stem cells and common lymphoid progenitors ; (3) Cre is expressed in more than 50% of all leukocytes. Hence, this study indicates that the reporter mice used to characterize Cre expression in Cre-driver mice should be selected with caution and considering the sensitivity of the reporter system. This study also suggests that the interpretation of some reports may need to be re-considered based on a careful evaluation of the cell type-specificity of Cre-mediated in their model.