TY  - JOUR
AU  - Waldt, Natalie
AU  - Kesseler, Christoph
AU  - Fala, Paula
AU  - John, Peter
AU  - Kirches, Elmar
AU  - Angenstein, Frank
AU  - Mawrin, Christian
TI  - Crispr/Cas-based modeling of NF2 loss in meningioma cells.
JO  - Journal of neuroscience methods
VL  - 356
SN  - 0165-0270
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2021-01185
SP  - 109141
PY  - 2021
AB  - 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.
KW  - Animals
KW  - Cell Line, Tumor
KW  - Clustered Regularly Interspaced Short Palindromic Repeats: genetics
KW  - Meningeal Neoplasms: genetics
KW  - Meningioma: genetics
KW  - Mice
KW  - Neurofibromin 2: genetics
KW  - Neurofibromin 2: metabolism
KW  - Crispr/Cas (Other)
KW  - Meningioma (Other)
KW  - Neurofibromatosis type 2 (NF2) (Other)
KW  - Neurofibromin 2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33753124
DO  - DOI:10.1016/j.jneumeth.2021.109141
UR  - https://pub.dzne.de/record/157728
ER  -