A widely used EYFP-based Cre reporter mouse line fails to detect a significant fraction of Cre+ T cells

The ability to manipulate the mouse genome has contributed heavily to countless discoveries in biology for several decades. The Cre/loxP system enables conditional and inducible deletion of virtually any sequences in the mouse. Because Cre expression does not always predict Cre activity and does not necessarily mirror expression of the endogenous gene(s) whose cis-acting genetic elements were used to construct a given Cre "driver" mouse line, Cre "reporter" mouse lines have been developed in which expression of Cre is signified by expression of one of a variety of fluorescent or otherwise easily detectable proteins, including EYFP, tdTomato, and βgal. It is shown here that one such widely utilized Cre reporter mouse line, which expresses EYFP following Cre-mediated recombination, fails to detect a significant fraction of Cre+ T cells, as detected with an otherwise identical tdTomato-expressing Cre reporter. Given the wide use of this and similar Cre reporter mouse lines, these findings have potentially significant implications for a diverse array of studies.