Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse.
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.
Kalamarides
Michel
M
INSERM U434, Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, 75010 Paris, France.
Niwa-Kawakita
Michiko
M
Leblois
Hélène
H
Abramowski
Vincent
V
Perricaudet
Michel
M
Janin
Anne
A
Thomas
Gilles
G
Gutmann
David H
DH
Giovannini
Marco
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001099:Arachnoid / Q000473:pathology / Q000502:physiology*; D020868:Gene Silencing; D005822:Genetic Vectors; D006720:Homozygote; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D025581:Neurofibromin 2 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D025581:Neurofibromin 2; D016159:Tumor Suppressor Protein p53