{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:48:09Z","timestamp":1789692489040,"version":"4.0.1"},"reference-count":93,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS104489"],"award-info":[{"award-number":["R01NS104489"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gilbert Family Foundation - Gene Therapy Initiative","award":["863943"],"award-info":[{"award-number":["863943"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>\n                    Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations of the\n                    <jats:italic>NF1<\/jats:italic>\n                    tumor suppressor gene resulting in the loss of function of neurofibromin, a GTPase-activating protein (GAP) for Ras. While the malignant manifestations of NF1 are associated with loss of heterozygosity of the residual WT allele, the nonmalignant neurodevelopmental sequelae, including autism spectrum disorder (ASD) and\/or attention deficit hyperactivity disorder (ADHD) are prevalent morbidities that occur in the setting of neurofibromin haploinsufficiency. We reasoned that augmenting endogenous levels of WT neurofibromin could serve as a potential therapeutic strategy to correct the neurodevelopmental manifestations of NF1. Here, we used a combination of genetic screening and genetically engineered murine models to identify a role for the F-box protein FBXW11 as a regulator of neurofibromin degradation. Disruption of\n                    <jats:italic>Fbxw11<\/jats:italic>\n                    , through germline mutation or targeted genetic manipulation in the nucleus accumbens, increased neurofibromin levels, suppressed Ras-dependent ERK phosphorylation, and corrected social learning deficits and impulsive behaviors in male\n                    <jats:italic>\n                      Nf1\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Our results demonstrate that preventing the degradation of neurofibromin is a feasible and effective approach to ameliorate the neurodevelopmental phenotypes in a haploinsufficient disease model.\n                  <\/jats:p>","DOI":"10.1172\/jci188932","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T14:00:34Z","timestamp":1751292034000},"source":"Crossref","is-referenced-by-count":4,"title":["A haploinsufficiency restoration strategy corrects neurobehavioral deficits in Nf1+\/\u2013 mice"],"prefix":"10.1172","volume":"135","author":[{"given":"Su Jung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Research Institute for Korean Medicine, Pusan National University, Yangsan-si, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi 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Psychiatry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Zucker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinHee","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbi","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana K.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Division of Hematology-Oncology, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA."},{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7655-657X","authenticated-orcid":true,"given":"Steven P.","family":"Angus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Division of Hematology-Oncology, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA."},{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA."},{"name":"Department of Pharmacology and Toxicology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Wade","family":"Clapp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Division of Hematology-Oncology, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA."},{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA."},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, 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