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000157728 0247_ $$2doi$$a10.1016/j.jneumeth.2021.109141
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000157728 037__ $$aDZNE-2021-01185
000157728 041__ $$aEnglish
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000157728 1001_ $$aWaldt, Natalie$$b0
000157728 245__ $$aCrispr/Cas-based modeling of NF2 loss in meningioma cells.
000157728 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2021
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000157728 520__ $$aAlterations of the neurofibromatosis type 2 gene (NF2) occur in more than fifty percent of sporadic meningiomas. Meningiomas develop frequently in the setting of the hereditary tumor syndrome NF2. Investigation of potential drug-based treatment options has been limited by the lack of appropriate in vitro and in vivo models.Using Crispr/Cas gene editing, of the malignant meningioma cell line IOMM-Lee, we generated a pair of cell clones characterized by either stable knockout of NF2 and loss of the protein product merlin or retained merlin protein (transfected control without gRNA).IOMM-Lee cells lacking NF2 showed reduced apoptosis and formed bigger colonies compared to control IOMM-Lee cells. Treatment of non-transfected IOMM-Lee cells with the focal adhesion kinase (FAK) inhibitor GSK2256098 resulted in reduced colony sizes. Orthotopic mouse xenografts showed the formation of convexity tumors typical for meningiomas with NF2-depleted and control cells.No orthotopic meningioma models with genetically-engineered cell pairs are available so far.Our model based on Crispr/Cas-based gene editing provides paired meningioma cells suitable to study functional consequences and therapeutic accessibility of NF2/merlin loss.
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000157728 650_7 $$2Other$$aCrispr/Cas
000157728 650_7 $$2Other$$aMeningioma
000157728 650_7 $$2Other$$aNeurofibromatosis type 2 (NF2)
000157728 650_7 $$2NLM Chemicals$$aNeurofibromin 2
000157728 650_2 $$2MeSH$$aAnimals
000157728 650_2 $$2MeSH$$aCell Line, Tumor
000157728 650_2 $$2MeSH$$aClustered Regularly Interspaced Short Palindromic Repeats: genetics
000157728 650_2 $$2MeSH$$aMeningeal Neoplasms: genetics
000157728 650_2 $$2MeSH$$aMeningioma: genetics
000157728 650_2 $$2MeSH$$aMice
000157728 650_2 $$2MeSH$$aNeurofibromin 2: genetics
000157728 650_2 $$2MeSH$$aNeurofibromin 2: metabolism
000157728 7001_ $$aKesseler, Christoph$$b1
000157728 7001_ $$aFala, Paula$$b2
000157728 7001_ $$aJohn, Peter$$b3
000157728 7001_ $$aKirches, Elmar$$b4
000157728 7001_ $$0P:(DE-2719)2810456$$aAngenstein, Frank$$b5$$udzne
000157728 7001_ $$aMawrin, Christian$$b6
000157728 773__ $$0PERI:(DE-600)1500499-5$$a10.1016/j.jneumeth.2021.109141$$gVol. 356, p. 109141 -$$p109141$$tJournal of neuroscience methods$$v356$$x0165-0270$$y2021
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