Tg(Cebpb-rtTA2S*S2)1Bjd

The transgene contains a cDNA with "humanized" codon usage translated from the amino acid sequence of a reverse tetracycline (tet) transactivator protein (rtTA2S-S2) that was derived by the following modifications of the tet transactivator (repressor) protein (tTA): Glu19Gly, in the DNA binding domain; Ala56Pro, in the fourth alpha helix connecting the DNA binding domain with the core region; Asp148Glu and His179Arg, in the core near the tet-binding and dimerization domains, respectively. Expression is driven by the promoter of the gene encoding CCAAT/enhancer binding protein (C/EBP), beta, also called liver-enriched activating protein. The polyadenylation signal and a 3' intron are derived from a beta-globin gene. Progeny of mice doubly transgenic for this transgene and a tetracycline-operator- (tetO-) regulated luciferase gene exhibit no or barely detectable luciferase induction in the absence of doxycycline (Dox). Dox administration results in a rapid rise in luciferase activity, reaching 3 and 5 orders of magnitude in liver and kidney, respectively; histologic examination of livers of bitransgenic mice with a tetO-regulated lacZ gene revealed X-gal staining of all hepatocytes. Induction in other organs, including spleen, lung, heart, skeletal muscle and brain, is minimal. (J:81196, J:99884)