Overexpression of Pax5 is not sufficient for neoplastic transformation of mouse neuroectoderm

The developmental control genes of the Pox family are essential for brain d evelopment. Several Pox genes are also involved in chromosomal translocatio ns causing malignancies in humans, and Pax5 expression is deregulated in me dulloblastomas, We have investigated whether Pax5 can induce tumors in the developing mouse brain. Primary mouse embryonic neuroectodermal cells were retrovirally transduced with mouse Pax5 and transplanted into the brain of syngeneic host mice. No tumors developed in 36 transplants after one year, and there were no alterations in the differentiation pattern of the neural transplants, We then generated transgenic mice expressing human Pax5 under control of the Engrailed-2 promoter, which is expressed in the cerebellar e xternal granule cell layer and in medulloblastomas. Sustained expression wa s achieved in the cerebellum of transgenic animals throughout lifetime. Exp ression levels were similar to those observed in human medulloblastomas, Ag ain, cerebellar morphogenesis was undisturbed, and no tumors arose. These r esults strongly argue against a dominant transforming activity of PAX5 in N EC and in cerebellar granule cell precursors of mice, and underline the res tricted tissue-specificity of PAX5 related oncogenesis. (C) 2001 Wiley-Liss , Inc.