Characterization of pheochromocytomas in a mouse strain with a targeted disruptive mutation of the neurofibromatosis gene Nf1

摘要: Patients with neurofibromatosis type 1 (NF1) show an increased frequency of pheochromocytomas. The NF1 gene encodes a GTPase-activating protein that controls the activity ras proteins in intracellular signaling. A mouse strain knockout mutation Nf1, murine counterpart NF1, has recently been constructed. This mutation, designated Nf1(n31), shown to be associated frequent development pheochromocytomas heterozygous animals. Pheochromocytomas are extremely rare wild-type mice. We have characterized tumors assess their relevance as model for human was determined inbred compared outbred mice carrying Nf1(31) mutation. Paraffin sections from seven were stained immunohistochemically catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), and phenylethanolamine-N-methyltransferase (PNMT) infer profiles synthesis, chromogranin (CGA) content secretory granules. Cultured cells representative tumor studied vitro proliferation neuronal differentiation. arose approx 15% Nf1(n31) mixed genetic background, but absent Approximately one-fourth bilateral. exhibited variable morphology. All included appeared well differentiated resembled normal chromaffin they expressed TH, PNMT, CGA. Focal differentiation also observed. In cell culture, ceased proliferate majority underwent terminal into TH-positive phenotype resembles pheochromocytomas, particularly respect ability produce epinephrine, inferred positive staining PNMT. resemble both neoplastic adrenal medulla extensive neuron-like vitro. change may related activation. These neoplasms valuable models pathobiology medullary neoplasia, source epinephrine-producing pheochromocytoma lines, which adequate currently do not exist.