Liang, Tsanyang (Jake) (NIDDK)
Tetracycline-responsive transcriptional activator driven by the liver-specific mouse albumin promoter (Alb-tTA).
The E. Coli tetracycline operon regulatory system was used to generate a liver-specific transcription activation system that was inhibited by tetracycline. The transcription activator was a fused protein consisting of a tetracycline repressor gene (tetR) that was only active in the presence of tetracycline and a herpes simplex virus protein (VP-16) transcription activating domain. Transcription was induced only in the absence of tetracycline (Tet-Off). A liver-specific promoter such as mouse albumin determined that the tetracycline-regulated transcriptional activator (tTA) would be expressed specifically in liver. To study the effect of the transcription activator on a target gene (for example, Simian Virus 40 (SV4) large tumor (T) antigen (TAg)) specifically in liver, Alb-tTA mice were mated with transgenic mice in which the Target gene (TAg) was controlled by the E.Coli Tetracycline Operator (Tet-O). In this example, TAg was expressed in hepatocytes in the absence of Tetracycline, leading to hepatoma formation. When the mice were treated with tetracycline, TAg was not expressed and hepatomas did not form.
Mouse model to liver function.