HIGHLY CONTROLLED GENE-EXPRESSION USING COMBINATIONS OF A TISSUE-SPECIFIC PROMOTER RECOMBINANT ADENOVIRUS AND A TETRACYCLINE-REGULATABLE TRANSCRIPTION FACTOR

Controllable gene expression is a desirable feature both in gene thera py protocols and for the study of gene function in animals and plants. We have exploited the modular character of the tetracycline (tc)-regu latable genetic switch to show that its components can be encoded by a ny combination of recombinant adenovirus and/or transgenic mice. Trans genic mice were constructed that express the tc-regulatable trans-acti vator tTA muscle specifically. These were injected with recombinant ad enovirus expressing a luciferase reporter controlled by the tTA-regula table promoter. Virus injected into muscle, but not into a control org an (brain) resulted in luciferase activity. Conversely, injection of t TA producing adenovirus into mice that were transgenic for a trkB/Fc f usion protein gene-under to promoter control resulted in swift express ion of serum trkB/Fc receptor-body. Both modes of gene induction were fully inhibited by administration of tc. We demonstrate that a careful choice of these fools allows exquisite in vivo control over transgene expression in a temporal, tc-regulatable, topical and tissue-specific manner.