title: Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein.
abstract: Specific mutations in some tumor suppressor genes such as p53 can act in a dominant fashion. We tested whether this mechanism may also apply for the neurofibromatosis type-2 gene (NF2) which, when mutated, leads to schwannoma development. Transgenic mice were generated that express, in Schwann cells, mutant NF2 proteins prototypic of natural mutants observed in humans. Mice expressing a NF2 protein with an interstitial deletion in the amino-terminal domain showed high prevalence of Schwann cell-derived tumors and Schwann cell hyperplasia, whereas those expressing a carboxy-terminally truncated protein were normal. Our results indicate that a subset of mutant NF2 alleles observed in patients may encode products with dominant properties when overexpressed in specific cell lineages.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U434-Institut Curie, 75005 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Giovannini
authors.forename: E
authors.initials: E
authors.lastname: Robanus-Maandag
authors.forename: M
authors.initials: M
authors.lastname: Niwa-Kawakita
authors.forename: M
authors.initials: M
authors.lastname: van der Valk
authors.forename: J M
authors.initials: JM
authors.lastname: Woodruff
authors.forename: L
authors.initials: L
authors.lastname: Goutebroze
authors.forename: P
authors.initials: P
authors.lastname: Mérel
authors.forename: A
authors.initials: A
authors.lastname: Berns
authors.forename: G
authors.initials: G
authors.lastname: Thomas
mesh_terms: D000818:Animals; D006801:Humans; D006965:Hyperplasia / Q000209:etiology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009442:Neurilemmoma / Q000209:etiology* / Q000473:pathology; D025581:Neurofibromin 2; D011817:Rabbits; D051381:Rats; D012583:Schwann Cells
chemical_list: D008565:Membrane Proteins; D025581:Neurofibromin 2