{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:24:35Z","timestamp":1781591075697,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Neurofibromatosis type 2 (\n Nf2<\/jats:italic>\n ) gene inactivation is common in sporadic and\n Nf2<\/jats:italic>\n \u2010related meningioma. There is currently scant literature describing the development of an intracranial meningioma model in animals. Given the role of\n Nf2<\/jats:italic>\n and other gene inactivation in meningeal cells, we used Cas9 mice here as the background host to establish a new animal model of skull base meningioma in this study.\n <\/jats:p>\n <\/jats:sec>\n \n Aims<\/jats:title>\n \n Cas9 transgenic mice were purchased from Jackson Laboratory and raised in our institution. Subsequently, meningeal cells were obtained from the Cas9 transgenic mice, cultured in medium, and passaged in\u00a0vitro. We then prepared lentivirus vector pLentiCre\/gRNA, which could express the elements blocking the function of four genes:\n Nf2, P15<\/jats:italic>\n \n Ink4b<\/jats:italic>\n <\/jats:sup>\n ,\n P16<\/jats:italic>\n \n Ink4a<\/jats:italic>\n <\/jats:sup>\n ,<\/jats:italic>\n and\n P19<\/jats:italic>\n \n Arf<\/jats:italic>\n <\/jats:sup>\n . We infected the meningeal cells with the lentivirus vector pLentiCre\/gRNA and tested the expression of these four genes in those infected meningeal cells. Next, adeno\u2010associated virus vector pAAVCre\/gRNA was injected in\u00a0vivo into the skull base meningeal cells of the neonate Cas9 transgenic mice. These mice were observed once a week and killed 10\u2009months later for brain inspection and pathological analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Twenty Cas9 transgenic mice were successfully bred. Five mice were killed so that meningeal cells could be extracted, cultured, and infected with the lentivirus vector pLentiCre\/gRNA for 72\u2009h in\u00a0vitro. The gene function test showed that\n Nf2, P15<\/jats:italic>\n \n Ink4b<\/jats:italic>\n <\/jats:sup>\n ,\n P16<\/jats:italic>\n \n Ink4a<\/jats:italic>\n <\/jats:sup>\n ,<\/jats:italic>\n and\n P19<\/jats:italic>\n \n Arf<\/jats:italic>\n <\/jats:sup>\n were all blocked in the infected meningeal cells, which indicated that the lentivirus vector pLentiCre\/gRNA could effectively block the expression of the four genes in targeted cells. Then pAAVCre\/gRNA was injected into the skull base meningeal cells of 15 mice in\u00a0vivo, and nine mice were observed for 10\u2009months so that the intracranial tumor growth could be assessed. Among these nine mice, pathological analysis showed that six mice had benign meningioma subtypes similar to human meningioma, one mouse had atypical meningioma, one mouse had malignant meningioma, and one mouse had sarcoma.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The Cas9 mouse model of skull base meningioma generated with the\n Nf2<\/jats:italic>\n genetic defect and the combinational loss of\n P15<\/jats:italic>\n \n Ink4b<\/jats:italic>\n <\/jats:sup>\n ,\n P16<\/jats:italic>\n \n Ink4a<\/jats:italic>\n <\/jats:sup>\n , and\n P19<\/jats:italic>\n \n Arf<\/jats:italic>\n <\/jats:sup>\n could provide a new tool for investigating the pathogenesis of meningioma and the development of chemical interventions for this disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cns.70287","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T06:47:40Z","timestamp":1740984460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cas9 Mouse Model of Skull Base Meningioma Driven by Combinational Gene Inactivation in Meningeal Cells"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1852-3128","authenticated-orcid":false,"given":"Hailiang","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Operation Center, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyang","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of 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