Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice

Transplantable tumors and cell lines have been developed from pheochromocyt omas arising in mice with a heterozygous knockout mutation of the neurofibr omatosis gene, Nf1. Nf1 encodes a ms-GTPase-activating protein, neurofibrom in, and mouse pheochromocytoma (MPC) cells in primary cultures typically sh ow extensive spontaneous neuronal differentiation that may result from the loss of the remaining wild-type allele and defective regulation of ras sign aling. However, all MPC cell lines express neurofibromin, suggesting that p reservation of the wild-type allele may be required to permit the propagati on of MPC cells in vitro. MPC lines differ from PC12 cells in that they exp ress both endogenous phenylethanolamine N-methyltransferase (PNMT) and full -length PNMT reporter constructs. PNMT expression is increased by dexametha sone and by cell-cell contact in suspension cultures. Mouse pheochromocytom as are a new tool for studying genes and signaling pathways that regulate c ell growth and differentiation in adrenal medullary neoplasms and are a uni que model for studying the regulation of PNMT expression.