02-P014 – Withdrawn

by a short BrdU pulse, indicating that prevention of Bmi1 downregulation does not drive granule cells back into the cell cycle. No tumours were observed in two aging cohorts of transgenic mice derived from separate founder lines. However, these mice display an increase in astrocytes with the type II morphology in vitro compared to wild-type littermates. Cultures of FACSorted Math1-GFP+ granule cells showed that the increase in astrocytes is not due to transdifferentiation of granule cells, but likely due to a cell extrinsic effect exerted by granule cells on glial progenitors in the cerebellum. Overexpression of Bmi1 in GCPs under the Math1 enhancer is also not sufficient to drive medulloblastoma formation. On the contrary, a reduction in cerebellar weight was observed. Abnormalities in cell death and cell proliferation are being investigated in these mice. In conclusion: high-level Bmi1 expression in postmitotic granule cells or in GCPs is not sufficient to initiate medulloblastoma development.