Tet-on / Tet-off (Doxycycline-Inducible Systems)

The tetracycline (Tet) systems provide doxycycline-dependent temporal control of gene expression, including of Cre itself. They are built from three elements: the reverse tetracycline-controlled transactivator (rtTA), the tetracycline-controlled transactivator (tTA), and the tetracycline responsive element (TRE, also called tetO7, seven repeats of a minimal tetO promoter) placed upstream of the gene to be controlled.

In the Tet-on configuration, rtTA can bind tetO7 and activate transcription only when bound to doxycycline, so adding the drug switches expression on. In Tet-off, tTA occupies tetO7 constitutively and doxycycline displaces it, so adding the drug switches expression off. Doxycycline, a tetracycline derivative, is usually delivered in feed or drinking water and is more cost-effective and more efficient at controlling the Tet repressor than tetracycline itself.