Mice transgenic for a tetracycline-inducible transcriptional activator

A transgenic mouse having a transgene integrated into the genome of the mouse and also having a tet operator-linked gene in the genome of the mouse, wherein:

• the transgene comprises a transcriptional regulatory element functional in cells of the mouse operatively linked to a polynucleotide sequence encoding a fusion protein which activates transcription of said tet operator-linked gene,
• the fusion protein comprises a first polypeptide which is a mutated Tet repressor that binds to a tet operator sequence in the presence of tetracycline or a tetracycline analogue operatively linked to a second polypeptide which activates transcription in eukaryotic cells,
• said tet operator-linked gene confers a detectable and functional phenotype on the mouse when expressed in cells of the mouse,
• said transgene is expressed in cells of the mouse at a level sufficient to produce amounts of said fusion protein that are sufficient to activate transcription of the tet operator-linked gene;
• and
• in the presence of tetracycline or a tetracycline analogue in the mouse, said fusion protein binds to the tet operator-linked gene and activates transcription of the tet operator linked gene such that the tet operator-linked gene is expressed at a level sufficient to confer the detectable and functional phenotype on the mouse, wherein the level of expression of the tet operator-linked gene cap be downmodulated by depleting tetracycline or a tetracycline analogue from the mouse.