METASTASIZING NEUROBLASTOMAS IN MICE TRANSGENIC FOR SIMIAN-VIRUS-40 LARGE-T (SV40T) UNDER THE OLFACTORY MARKER PROTEIN GENE PROMOTER

The olfactory marker protein (OMP) is a M(r) 19,000 polypeptide origin ally considered a selective marker for differentiated olfactory recept or neurons. In an attempt to induce neoplastic proliferation in the ol factory cells, me made mice transgenic for the simian virus 40 large T -antigen gene linked to the OMP gene promoter. Four independent lines of transgenic mice mere established. Despite a high expression of the transgene in the olfactory receptor neurons, no evidence of tumor grow th was observed. Instead, starting from an age of 4 months, animals of all four lines presented with highly metastatic tumors originating in the adrenal medullas or sympathetic ganglia. The histological, ultras tructural, and immunohistochemical features of the tumors mere identic al to those of human infant neuroblastoma. Five independent neuroblast oma cell lines mere established from tumors of different transgenic an imals. All cell lines constitutively express the endogenous OMP gene. The transgene product, simian virus 40 large T-antigen, associates wit h the product of the antioncogene p53 in these cell lines. This transg ene system not only offers a biologically faithful model for investiga tions on the pathogenesis of neuroblastoma, the most common solid neop lasia of infancy, it also raises intriguing questions about the role o f the OMP gene for the differentiation of the sympathetic neurons.