{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:11:38Z","timestamp":1790017898339,"version":"4.0.1"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":35,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["P30 CA016086"],"award-info":[{"award-number":["P30 CA016086"]}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS131615"],"award-info":[{"award-number":["R01NS131615"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS129914"],"award-info":[{"award-number":["R01NS129914"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["1S10OD030300"],"award-info":[{"award-number":["1S10OD030300"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"name":"North Carolina Biotech Center","award":["2016-IDG-1016"],"award-info":[{"award-number":["2016-IDG-1016"]}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["P30 NS045892"],"award-info":[{"award-number":["P30 NS045892"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["P50 HD103573"],"award-info":[{"award-number":["P50 HD103573"]}]},{"DOI":"10.13039\/100001951","name":"Angelman Syndrome Foundation","doi-asserted-by":"crossref","award":["No grant number assigned"],"award-info":[{"award-number":["No grant number assigned"]}],"id":[{"id":"10.13039\/100001951","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:p>\n                    Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternal\n                    <jats:italic>UBE3A<\/jats:italic>\n                    allele, the sole source of UBE3A in mature neurons owing to epigenetic silencing of the paternal allele. Although emerging therapies are being developed to restore UBE3A expression by activating the dormant paternal\n                    <jats:italic>UBE3A<\/jats:italic>\n                    allele, existing mouse models for such preclinical studies have limited throughput and utility, creating bottlenecks for both in vitro therapeutic screening and in vivo characterization. To address this, we developed the\n                    <jats:italic>Ube3a<\/jats:italic>\n                    -INSG dual-reporter knockin mouse, in which an IRES-Nanoluciferase-T2A-Sun1-sfGFP (INSG) cassette was inserted downstream of the endogenous\n                    <jats:italic>Ube3a<\/jats:italic>\n                    stop codon. The INSG model preserves UBE3A protein levels and function while enabling 2 complementary allele-specific readouts: Sun1-sfGFP and Nanoluciferase. We show that Sun1-sfGFP, a nuclear envelope\u2013localized reporter, enables single-cell fluorescence analysis, whole-brain light-sheet imaging, and nuclear quantification by flow cytometry. Further, Nanoluciferase supports high-throughput luminescence assays for sensitive pharmacological profiling in cultured neurons and noninvasive in vivo bioluminescence imaging for pharmacodynamic assessment. By combining scalable screening, cellular analysis, and real-time in vivo monitoring in a single model, the\n                    <jats:italic>Ube3a<\/jats:italic>\n                    -INSG dual-reporter mouse provides a powerful platform to accelerate therapeutic development centered on UBE3A.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.197028","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:57:23Z","timestamp":1770145043000},"source":"Crossref","is-referenced-by-count":2,"title":["A dual-reporter mouse for therapeutic discovery in Angelman syndrome"],"prefix":"10.1172","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6128-636X","authenticated-orcid":true,"given":"Hanna","family":"Vihma","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas M.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Nourie","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlee A.","family":"Friar","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasmai","family":"Vulli","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale O.","family":"Cowley","sequence":"additional","affiliation":[{"name":"Animal Models Core,"},{"name":"Department of Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain C.","family":"Burette","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-9143","authenticated-orcid":true,"given":"Benjamin D.","family":"Philpot","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Neuroscience Center,"},{"name":"Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.17305\/bb.2025.11724"},{"issue":"3\u20135","key":"B2","first-page":"100","article-title":"Molecular and clinical aspects of Angelman syndrome","volume":"2","author":"Dagli","year":"2012","journal-title":"Mol Syndromol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-025-03551-4"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-70"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-74"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401302200"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-12"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2023.2245568"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature10726"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49788-8"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.02.004"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf4077"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf851"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature13975"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145991"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.01.013"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142574"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2835-2"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-08794-2"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.02.015"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm288"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23507"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1634-20.2020"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.113684"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1665693"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1101\/lm.032375.113"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80596-6"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0037-17.2017"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-024-00636-y"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0231-7"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034115"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.018"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10874"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-017-0134-4"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg106"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2024.1410791"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1021\/jm0408870"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.010"},{"key":"B39"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202403130RR"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2217\/epi.15.70"},{"issue":"4","key":"B42","first-page":"928","article-title":"Autism or atypical autism in maternally but not paternally derived proximal 15q duplication","volume":"60","author":"Eh","year":"1997","journal-title":"Am J Hum Genet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.08.011"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005993"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158953"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.02.002"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx289"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22800"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6793-3-8"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.09.003"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.03.021"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106651"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2025.106882"},{"key":"B54","doi-asserted-by":"crossref","unstructured":"Goldsborough T, et al. A novel channel invariant architecture for the segmentation of cells and nuclei in multiplexed images using InstanSeg [preprint]. https:\/\/doi.org\/10.1101\/2024.09.04.611150 Posted on bioRxiv September 8, 2024","DOI":"10.1101\/2024.09.04.611150"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13374-0"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.007"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112706"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81892"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.03.051"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1021\/jm031145u"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060310"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1042\/NS20180207"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100844"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/197028\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:29:35Z","timestamp":1778873375000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/197028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":64,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,1,27]]},"published-print":{"date-parts":[[2026,3,9]]}},"alternative-id":["10.1172\/jci.insight.197028"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.197028","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"article-number":"e197028"}}