Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein.
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.
Giovannini
M
M
Institut National de la Santé et de la Recherche Médicale (INSERM) U434-Institut Curie, 75005 Paris, France.
Robanus-Maandag
E
E
Niwa-Kawakita
M
M
van der Valk
M
M
Woodruff
J M
JM
Goutebroze
L
L
Mérel
P
P
Berns
A
A
Thomas
G
G
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
D008565:Membrane Proteins; D025581:Neurofibromin 2