{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:23Z","timestamp":1792790363601,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,16]]},"group-title":"Cancer Biology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"United States Army Medical Research and Development Command","award":["W81XWH-21-1-0446"],"award-info":[{"award-number":["W81XWH-21-1-0446"]}],"id":[{"id":"https:\/\/ror.org\/03cd02q50","id-type":"ROR","asserted-by":"crossref"}]},{"name":"United States Army Medical Research and Development Command","award":["W81XWH-21-1-0448"],"award-info":[{"award-number":["W81XWH-21-1-0448"]}],"id":[{"id":"https:\/\/ror.org\/03cd02q50","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    Patients with\n                    <jats:italic>NF2<\/jats:italic>\n                    -related schwannomatosis (\n                    <jats:italic>NF2<\/jats:italic>\n                    -SWN) present with hallmark bilateral vestibular schwannomas, but also schwannomas on other cranial, spinal, and peripheral nerves, as well as meningiomas and ependymomas, caused by germline mutations in the tumor suppressor gene\n                    <jats:italic>NF2<\/jats:italic>\n                    . Current therapies involving surgery and radiosurgery are effective for individual tumors but are not always a viable option for patients with multiple tumors, and harbor significant risk of neurological deficits and morbidity. Gene replacement therapy is becoming a promising new treatment strategy for several neurologic diseases. This study aims to understand if restoration of a functional merlin protein, gene product of the\n                    <jats:italic>Nf2<\/jats:italic>\n                    gene, in\n                    <jats:italic>Nf2<\/jats:italic>\n                    -deficient tumor cells, can provide preclinical therapeutic efficacy in a\n                    <jats:italic>NF2<\/jats:italic>\n                    -SWN genetically engineered mouse model.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We have developed a new\n                    <jats:italic>Nf2<\/jats:italic>\n                    allele (\n                    <jats:italic>Nf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>FRT<\/jats:italic>\n                    <\/jats:sup>\n                    ) that allows to conditionally restore\n                    <jats:italic>Nf2<\/jats:italic>\n                    expression by activation with the Flp recombinase. We generated a new mouse model using the\n                    <jats:italic>Nf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>FRT<\/jats:italic>\n                    <\/jats:sup>\n                    allele in combination with\n                    <jats:italic>Nf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>Postn-Cre<\/jats:italic>\n                    alleles.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Using the new conditional schwannoma mouse model\n                    <jats:italic>Postn-Cre;Nf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>FRT\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>;R26<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>FlpoER<\/jats:italic>\n                    <\/jats:sup>\n                    , we validated the hypothesis that restoration of\n                    <jats:italic>Nf2<\/jats:italic>\n                    reduces the growth of schwannoma.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    Demonstrating that merlin restoration effectively controls schwannoma growth is a crucial first step toward developing this concept as a new therapeutic strategy for potentially treating schwannomas. The new mouse model will be used to better understand the cellular and molecular mechanisms involved in stopping the growth of\n                    <jats:italic>Nf2<\/jats:italic>\n                    -deficient tumors.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.12.751200","type":"posted-content","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:35:12Z","timestamp":1789569312000},"source":"Crossref","is-referenced-by-count":0,"title":["Merlin restoration prevents schwannoma progression in a genetically engineered mouse model of\n                  <i>NF2<\/i>\n                  -SWN"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-7988","authenticated-orcid":false,"given":"Jeremie","family":"Vitte","sequence":"first","affiliation":[{"name":"Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center (JCCC), University of California Los Angeles, 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