Transgenesis in mice has become a useful tool to study gene function and model human diseases in vivo. Examples of transgenic mouse strains generated to study oncogenesis in the haematopoietic system include, amongst others, mice overexpressing anti-apoptotic Bcl-2 to model follicular B cell lymphomas, a mutated version of N-Ras driving T cell and histocytic lymphomagenesis, the BCR-abl fusion protein driving chronic myelocytic leukemia and cases of acute myelocytic leukemia in humans or the c-Myc proto-oncogene under the control of the Igheavy chain enhancer that develop aggressive preB and IgM + B cell lymphomas, mimicking to a certain degree features of Burkitt lymphoma. Although transgenic mice are suitable models to study a variety of pathological states, certain restrictions apply. One of the problems connected with Atropine transgene overexpression is putative cytotoxicity, sometimes associated with induced lethality, but more frequently silencing of transgene expression and counter-selection of cells with low or no transgene expression. Another limitation is related to the fact that expression of the target gene may be only Amsacrine hydrochloride desired in a specific cell type, at a specific developmental stage or for a limited time frame to better mimic events during normal development or human disease pathology. To overcome these problems, tissue specific transgenesis has been developed that aims to exploit certain regulated gene-expression systems derived from bacteria, e.g. the tetracycline-based TetON/OFF system developed by Bujard and colleagues, or, for nuclear acting transgenes such as Cre recombinase, estrogen-receptor -fusion proteins that can be retained in the cytoplasm and translocate into the nucleus upon application of the synthetic ligand, 4-hydroxytamoxifen. Although well established in cell lines and today frequently used in transgenic mouse strains, certain limitations apply to these systems, mainly insufficient tightness of gene-repression and/or moderate induction levels, e.g., due to ineffective delivery and targeting of agonists to the cell type/tissue of interest, as well as stochastic epigenetic transgene silencing. Therefore, we aimed to combine a tissue-specific transgene expression system with an inducible one that would allow regulated transgenesis in the haematopoietic system.