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024 7 _ |a 10.1016/j.jneumeth.2021.109141
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082 _ _ |a 610
100 1 _ |a Waldt, Natalie
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245 _ _ |a Crispr/Cas-based modeling of NF2 loss in meningioma cells.
260 _ _ |a Amsterdam [u.a.]
|c 2021
|b Elsevier Science
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520 _ _ |a 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.
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650 _ 7 |a Crispr/Cas
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650 _ 7 |a Meningioma
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650 _ 7 |a Neurofibromatosis type 2 (NF2)
|2 Other
650 _ 7 |a Neurofibromin 2
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Clustered Regularly Interspaced Short Palindromic Repeats: genetics
|2 MeSH
650 _ 2 |a Meningeal Neoplasms: genetics
|2 MeSH
650 _ 2 |a Meningioma: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neurofibromin 2: genetics
|2 MeSH
650 _ 2 |a Neurofibromin 2: metabolism
|2 MeSH
700 1 _ |a Kesseler, Christoph
|b 1
700 1 _ |a Fala, Paula
|b 2
700 1 _ |a John, Peter
|b 3
700 1 _ |a Kirches, Elmar
|b 4
700 1 _ |a Angenstein, Frank
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700 1 _ |a Mawrin, Christian
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773 _ _ |a 10.1016/j.jneumeth.2021.109141
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|t Journal of neuroscience methods
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|x 0165-0270
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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