Tetracyclines in the control of gene expression in eukaryotes

The potential to conditionally alter the activity of individual genes in complex genetic systems and to observe accompanying phenotypic changes has provided new insights into numerous biological processes hitherto not amenable to genetic dissection. The most widely applied approach makes use of a transcriptional regulation system which allows stringent control of gene expression by tetracycline (Tc) or its derivative doxycycline (Dox). The various versions of the "Tet regulatory system" were successfully incorporated into a variety of cultured cells but, most interestingly, they were also shown to function in many biological model organisms such asS. cerevisiae Dictyostelium Drosophila Arabidopsismice and rats. Thus they have developed into an efficient tool for the study of gene functionin vivo. In particular for the mouse, which has become a widely used model for mammalian genetics thanks to transgenesis and embryonic stem cell technology, the advent of a generally applicable conditional gene expression system adds another level of sophistication for the dissection of gene function [1 2]. Indeed, exploiting the Tet regulatory systemsin vivo is beginning to provide fundamental insights into such complex biological processes as development, disease and behaviour [3 4 5 6 7 8 9 10]. Moreover, as tetracyclines are non-toxic compounds extensively used in human and animal medicine, the Tet regulatory systems may even hold promise in gene therapy.