Endogenous hormones cannot induce the transactivator, but RU486 effectively activates the transactivator by promoting the binding of GAL4 DNA-binding domain to its consensus elements. Transgenic mice have been established that express the transactivator, as well as a human growth hormone (hGH) gene driven by 4 GAL4 DNA-binding sequences upstream of a TATA box. Only mice given RU486 express hGH, and the transgene can be induced rapidly, within 12 hours of RU486 administration. This system suffers from slow de-induction in vivo, taking up to 100 hours to reach uninduced basal expression (7). In mice expressing erythropoietin (Epo) under control of the PRS or TrRS, the limitation of the latter system becomes apparent: Hematocrit levels of mice could be conveniently up-and downregulated by doxycycline (Dox) but were hardly reversible on withdrawing RU486 administration. The slow de-induction of PRS is a consequence of the long half-life of RU486 and its poor diffusion within tissues (10). The PRS is also efficient as a self-contained unit, producing about 150-fold regulation when delivered on a recombinant herpes simplex virus (11). Burcin et al.(12) recently developed a