Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein
- Marco Giovannini,
- Els Robanus-Maandag,
- Michiko Niwa-Kawakita,
- Martin van der Valk,
- James M. Woodruff,
- Laurence Goutebroze,
- Philippe Mérel,
- Anton Berns, and
- Gilles Thomas
- Institut National de la Santé et de la Recherche Médicale (INSERM) U434–Institut Curie, 75005 Paris, France; Centre d’Etude du Polymorphisme Humain (CEPH) Fondation Jean Dausset, 75010 Paris, France; Division of Molecular Genetics and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 USA
Abstract
Specific mutations in some tumor suppressor genes such asp53 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.
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Footnotes
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↵Corresponding author.
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E-MAIL thomas{at}cephb.fr; FAX 33 1 53 72 51 51.
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- Received October 20, 1998.
- Accepted February 25, 1999.
- Cold Spring Harbor Laboratory Press
