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pageSummary
Promoters whose temporal activity can be directly manipulated in transgenic
animals provide a tool for the study of gene functions in vivo. We have evaluated a
tetracycline responsive binary system for its ability to temporally control gene
expression in transgenic mice. In this system, a transactivator protein (tTA), composed of
the repressor of the tetracycline operon (tetR)from E. coli (Tn 10) and the activating
domain of the herpes simplex virus protein 16 (HSV-VP16), induces transcription from a
minimal promoter fused to seven tet operator (tetO) sequences (PHCMV*-1) in the absence of
tetracycline, but not in its presence (1). Transgenic mice were generated that carried
either a luciferase or a b-galactosidase reporter gene under the control of PHCMV*-1, or a
transgene containing the tTA coding sequence under the control of the human
cytomegalovirus immediate early 1 (HCMV IE1) promoter enhancer. Whereas little luciferase
or b-galactosidase activity was observed in tissues of mice carrying only the reporter
genes, the presence of tTA in double transgenic mice induced expression of the reporter
genes up to several thousand-fold. This induction was abrogated to basal levels upon
administration of tetracycline. These findings can be used, for example, to design
dominant gain of function experiments in which temporal control of transgene expression is
required.
Key Citations
Priscilla A. Furth, Luc St. Onge, Hinrich Böger, Peter Gruss, Manfred Gossen, Andreas
Kistner, Hermann Bujard and Lothar Hennighausen (1994) Temporal control of gene expression
in transgenic mice by a tetracycline responsive promoter.
Submitted
by Lothar Hennighausen(e-mail mammary@nih.gov)
last update: June 1998
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