Journal Article

DZNE-2021-01185

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Crispr/Cas-based modeling of NF2 loss in meningioma cells.

Waldt, N. ; Kesseler, C. ; Fala, P. ; John, P. ; Kirches, E. ; Angenstein, F.DZNE* ; Mawrin, C.

2021
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jneumeth.2021.109141

Abstract: 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.

Keyword(s): Animals (MeSH) ; Cell Line, Tumor (MeSH) ; Clustered Regularly Interspaced Short Palindromic Repeats: genetics (MeSH) ; Meningeal Neoplasms: genetics (MeSH) ; Meningioma: genetics (MeSH) ; Mice (MeSH) ; Neurofibromin 2: genetics (MeSH) ; Neurofibromin 2: metabolism (MeSH) ; Crispr/Cas ; Meningioma ; Neurofibromatosis type 2 (NF2) ; Neurofibromin 2

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Contributing Institute(s):

1. Functional Neuroimaging (AG Angenstein)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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