Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum

摘要: Medulloblastomas are among the most common malignancies in childhood, and they associated with substantial mortality morbidity. The molecular pathogenesis as well ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre–LoxP-mediated inactivation Rb p53 tumor suppressor genes cerebellar external granular layer (EGL) cells. GFAP–Cre-mediated recombination was found both astrocytes immature precursor cells EGL developing cerebellum. GFAP–Cre;RbLoxP/LoxP;p53−/− or LoxP/LoxP mice developed highly aggressive embryonal tumors cerebellum typical features medulloblastoma. These were identified early 7 weeks age on outer surface layer, corresponding to location during development. Our results demonstrate that loss function RB essential development strongly support hypothesis medulloblastomas arise from multipotent located EGL.