Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2

Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is inactivated. We report that conditional homozygous Nf2 knocko...

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Published inGenes & development Vol. 14; no. 13; pp. 1617 - 1630
Main Authors Giovannini, M, Robanus-Maandag, E, van der Valk, M, Niwa-Kawakita, M, Abramowski, V, Goutebroze, L, Woodruff, J M, Berns, A, Thomas, G
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.07.2000
Subjects
Alleles
Animals
Base Sequence
DNA Primers
Exons
Gene Deletion
Genes, Neurofibromatosis 2
Humans
Life Sciences
Mice
Mice, Knockout
Mice, Transgenic
Mutation
Neurilemmoma
Neurilemmoma - genetics
Neurobiology
Neurofibromatosis 2
Neurofibromatosis 2 - genetics
Neurons and Cognition
Nf2 gene
Promoter Regions, Genetic
Research Paper
schwannoma
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Summary:Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is inactivated. We report that conditional homozygous Nf2 knockout mice with Cre-mediated excision of Nf2 exon 2 in Schwann cells showed characteristics of neurofibromatosis type 2. These included schwannomas, Schwann cell hyperplasia, cataract, and osseous metaplasia. Thus, the tumor suppressor function of Nf2, here revealed in murine Schwann cells, was concealed in hemizygous Nf2 mice because of insufficient rate of second allele inactivation in this cell compartment. The finding of this conserved function documents the relevance of the present approach to model the human disease.
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PMCID: PMC316733
These authors contributed equally to this work.
Corresponding author.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.14.13.1617