E2F-1 FUNCTIONS IN MICE TO PROMOTE APOPTOSIS AND SUPPRESS PROLIFERATION

Members of the E2F transcription factor family (E2F-1-E2F-5) are belie ved to be critical positive regulators of cell cycle progression in eu karyotes although the in vivo functions of the individual E2Fs have no t been elucidated. Mice were generated that lack E2F-1 and, surprising ly, these mice develop and reproduce normally. However, E2F-1(-/-) mic e exhibit a defect in T lymphocyte development leading to an excess of mature T cells due to a maturation stage-specific defect in thymocyte apoptosis. As E2F-1(-/-) mice age they exhibit a second phenotype mar ked by aberrant cell proliferation. These findings suggest that while certain members of the E2F family may positively regulate cell cycle p rogression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation.