Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse (original) (raw)
- Michel Kalamarides1,
- Michiko Niwa-Kawakita1,
- Hélène Leblois2,
- Vincent Abramowski1,
- Michel Perricaudet2,
- Anne Janin3,
- Gilles Thomas1,
- David H. Gutmann4, and
- Marco Giovannini1,5
- 1INSERM U434, Fondation Jean Dausset–Centre d'Etude du Polymorphisme Humain, 75010 Paris, France; 2UMR1582 Institut Gustave Roussy, 94805 Villejuif, France; 3Laboratory of Pathology INSERM ERIT-M 0209, 75010 Paris, France;4Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA
Abstract
Biallelic NF2 gene inactivation is common in sporadic and in neurofibromatosis type 2 (NF2)-related meningiomas. We show that, beginning at four months of age, thirty percent of mice with arachnoidal cell Cre-mediated excision of Nf2 exon 2 developed a range of meningioma subtypes histologically similar to the human tumors. Additional hemizygosity for p53 did not modify meningioma frequency or progression suggesting that Nf2 and_p53_ mutations do not synergize in meningeal tumorigenesis. This first mouse model initiated with a genetic lesion found in human meningiomas provides a powerful tool for investigating tumor progression and for the preclinical evaluation of therapeutic interventions.
Footnotes
↵5 Corresponding author.
E-MAIL marco{at}cephb.fr; FAX 33-1-5372-5192.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.226302.
- Received January 25, 2002.
- Accepted March 27, 2002.
Cold Spring Harbor Laboratory Press