%0 Journal Article
%A Waldt, Natalie
%A Kesseler, Christoph
%A Fala, Paula
%A John, Peter
%A Kirches, Elmar
%A Angenstein, Frank
%A Mawrin, Christian
%T Crispr/Cas-based modeling of NF2 loss in meningioma cells.
%J Journal of neuroscience methods
%V 356
%@ 0165-0270
%C Amsterdam [u.a.]
%I Elsevier Science
%M DZNE-2021-01185
%P 109141
%D 2021
%X Alterations of the neurofibromatosis type 2 gene (NF2) occur in more than fifty percent of sporadic meningiomas. Meningiomas develop frequently in the setting of the hereditary tumor syndrome NF2. Investigation of potential drug-based treatment options has been limited by the lack of appropriate in vitro and in vivo models.Using Crispr/Cas gene editing, of the malignant meningioma cell line IOMM-Lee, we generated a pair of cell clones characterized by either stable knockout of NF2 and loss of the protein product merlin or retained merlin protein (transfected control without gRNA).IOMM-Lee cells lacking NF2 showed reduced apoptosis and formed bigger colonies compared to control IOMM-Lee cells. Treatment of non-transfected IOMM-Lee cells with the focal adhesion kinase (FAK) inhibitor GSK2256098 resulted in reduced colony sizes. Orthotopic mouse xenografts showed the formation of convexity tumors typical for meningiomas with NF2-depleted and control cells.No orthotopic meningioma models with genetically-engineered cell pairs are available so far.Our model based on Crispr/Cas-based gene editing provides paired meningioma cells suitable to study functional consequences and therapeutic accessibility of NF2/merlin loss.
%K Animals
%K Cell Line, Tumor
%K Clustered Regularly Interspaced Short Palindromic Repeats: genetics
%K Meningeal Neoplasms: genetics
%K Meningioma: genetics
%K Mice
%K Neurofibromin 2: genetics
%K Neurofibromin 2: metabolism
%K Crispr/Cas (Other)
%K Meningioma (Other)
%K Neurofibromatosis type 2 (NF2) (Other)
%K Neurofibromin 2 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33753124
%R 10.1016/j.jneumeth.2021.109141
%U https://pub.dzne.de/record/157728