{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:29:39Z","timestamp":1788881379740,"version":"build-2803163510"},"reference-count":43,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35NS111564"],"award-info":[{"award-number":["R35NS111564"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"crossref","award":["21-24018"],"award-info":[{"award-number":["21-24018"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Horizon 2020","award":["897949"],"award-info":[{"award-number":["897949"]}]},{"DOI":"10.13039\/100006961","name":"California Institute of Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006961","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a\/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displayed lower expression levels. Induction of nf2a\/b knockout at early stages increased the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a\/b knockout triggered the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.<\/jats:p>","DOI":"10.1242\/dmm.050862","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T07:11:09Z","timestamp":1729149069000},"source":"Crossref","is-referenced-by-count":7,"title":["Generation of a zebrafish neurofibromatosis model via inducible knockout of <i>nf2a\/b<\/i>"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0173-0465","authenticated-orcid":false,"given":"Ayyappa Raja","family":"Desingu Rajan","sequence":"first","affiliation":[{"name":"California Institute of Technology 1 Division of Biology and Biological Engineering , , Pasadena, CA 91125 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyun","family":"Huang","sequence":"additional","affiliation":[{"name":"California Institute of Technology 1 Division of Biology and Biological Engineering , , Pasadena, CA 91125 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stundl","sequence":"additional","affiliation":[{"name":"California Institute of Technology 1 Division of Biology and Biological Engineering , , Pasadena, CA 91125 ,","place":["USA"]},{"name":"University of South Bohemia in Ceske Budejovice 2 Faculty of Fisheries and Protection of Waters , , 38925 Vodnany ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Chu","sequence":"additional","affiliation":[{"name":"California Institute of Technology 1 Division of Biology and Biological Engineering , , Pasadena, CA 91125 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushka","family":"Irodi","sequence":"additional","affiliation":[{"name":"California Institute of Technology 1 Division of Biology and Biological Engineering , , Pasadena, CA 91125 ,","place":["USA"]},{"name":"University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital NHS Foundation Trust 3 , Cambridge CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Yang","sequence":"additional","affiliation":[{"name":"University of Southern California 4 , Caruso Department of Otolaryngology-Head and Neck Surgery, Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Applegate","sequence":"additional","affiliation":[{"name":"University of Southern California 4 , Caruso Department of Otolaryngology-Head and Neck Surgery, Los Angeles, CA 90033 ,","place":["USA"]},{"name":"University of Southern California 5 , Alfred Mann Department of Biomedical Engineering, Los Angeles, CA 90089 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne E.","family":"Bronner","sequence":"additional","affiliation":[{"name":"California Institute of Technology 1 Division of Biology and Biological Engineering , , Pasadena, CA 91125 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"2024120413340896000_DMM050862C1","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1002\/dvdy.20883","article-title":"Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic development","volume":"235","author":"Akhmametyeva","year":"2006","journal-title":"Dev. 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Genet."},{"key":"2024120413340896000_DMM050862C5","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41587-019-0032-3","article-title":"CRISPResso2 provides accurate and rapid genome editing sequence analysis","volume":"37","author":"Clement","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"2024120413340896000_DMM050862C6","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s00401-019-02029-5","article-title":"An update on the CNS manifestations of neurofibromatosis type 2","volume":"139","author":"Coy","year":"2020","journal-title":"Acta Neuropathol."},{"key":"2024120413340896000_DMM050862C7","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1177\/002215549904701113","article-title":"Expression of the neurofibromatosis type 2 gene in human tissues","volume":"47","author":"den Bakker","year":"1999","journal-title":"J. Histochem. 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