Tetracyclines gene switch

Unlike the Gre/loxP system, the tetR/O switch is not dependent on enzyme-based DNA rearrangements but is controlled by the small synthetic compound doxycycline (Dox). In the absence of Dox the tetracycline repressor (tetR), expressed from a constitutive promoter, binds to the tet operator (tetO) within a modified HI promoter and blocks shRNA transcription (Fig. 3b). Exposure to Dox dissociates the tetR from tetO which enables shRNA expression from the HI promoter (22). Thus, gene silencing is induced by Dox addition (20, 22, 23). This system is successfully in use to validate the potential of candidate drug targets in vivo (24-28). A commercial service for the production of Dox inducible knockdown mice and rats is available from Taconic (see www. taconic.com). 

The utility of the system has been fuither enhanced by repositioning one of the tet control elements, so that tetracycline can be used either as a positive or negative effector (i.e., for switching on or ofiF) of the gene to be controlled (15). When controlling the... 

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