Tg(Scgb1a1-rtTA,-tTS,tetO-TGFB1*)1Eli

The CC10-rtTA-hGH construct contains the CC10 promoter, the reverse tetracycline transactivation (rtTA), and human growth hormone (hGH) intronic and polyadenylation sequences. The tet-O-CMV-Tgfb1-SV40, contains a polymeric tetracycline operator (tet-O), minimal cytomegalovirus (CMV) promoter, human Tgfb1 cDNA in which the cysteine codons at positions 223 and 225 were replaced with serine codons, and SV40 polyadenylation signals. The third construct, CC10-tTS-hGH, has the CC10 promoter driving the expression of the tetracycline-controlled transcriptional silencer (tTS). All three constructs were coinjected into fertilized oocytes, and triple positive founder animals were obtained. In this system, the CC10 promoter constitutively drives the expression of rtTA and tTS in a lung-specific fashion. In the absence of dox, tTS binds to and actively suppresses the expression of the tet-Oregulated TGF-beta1 transgene. In the presence of dox, tTS is released allowing the activating, dox binding rtTA to bind the tet-O and activate transgene expression. (J:92469)