{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:03:36Z","timestamp":1791299016993,"version":"4.1.0"},"reference-count":75,"publisher":"American Society for Clinical Investigation","issue":"20","funder":[{"DOI":"10.13039\/100000135","name":"NIH Blueprint for Neuroscience Research","doi-asserted-by":"crossref","award":["MH098114"],"award-info":[{"award-number":["MH098114"]}],"id":[{"id":"10.13039\/100000135","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000135","name":"NIH Blueprint for Neuroscience Research","doi-asserted-by":"crossref","award":["MH104316"],"award-info":[{"award-number":["MH104316"]}],"id":[{"id":"10.13039\/100000135","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,19]]},"abstract":"<jats:p>\n                    Genetic defects in the synaptic scaffolding protein gene,\n                    <jats:italic>SHANK2<\/jats:italic>\n                    , are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of\n                    <jats:italic>SHANK2<\/jats:italic>\n                    mutations are poorly understood. We generated and characterized a line of\n                    <jats:italic>Shank2<\/jats:italic>\n                    mutant mice by deleting exon 24 (\u0394e24).\n                    <jats:italic>Shank2<\/jats:italic>\n                    <jats:sup>\u0394e24\u2013\/\u2013<\/jats:sup>\n                    mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors. While these phenotypes recapitulate the pleotropic behaviors associated with human\n                    <jats:italic>SHANK2-<\/jats:italic>\n                    related disorders, major behavioral features in these mice are reminiscent of bipolar disorder. For instance, their hyperactivity was augmented with amphetamine but was normalized with the mood stabilizers lithium and valproate.\n                    <jats:italic>Shank2<\/jats:italic>\n                    deficiency limited to the forebrain recapitulated the bipolar mania phenotype. The composition and functions of NMDA and AMPA receptors were altered at\n                    <jats:italic>Shank2<\/jats:italic>\n                    -deficient synapses, hinting toward the mechanism underlying these behavioral abnormalities. Human genetic findings support construct validity, and the behavioral features in\n                    <jats:italic>Shank2<\/jats:italic>\n                    \u0394e24 mice support face and predictive validities of this model for bipolar mania. Further genetic studies to understand the contribution of\n                    <jats:italic>SHANK2<\/jats:italic>\n                    deficiencies in bipolar disorder are warranted.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.92052","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T11:00:36Z","timestamp":1508324436000},"source":"Crossref","is-referenced-by-count":64,"title":["Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers"],"prefix":"10.1172","volume":"2","author":[{"given":"Andrea L.","family":"Pappas","sequence":"first","affiliation":[{"name":"Department of Neurobiology,"},{"name":"Cellular and Molecular Biology Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra L.","family":"Bey","sequence":"additional","affiliation":[{"name":"Department of Neurobiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Neurobiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidun","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Porkka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara J.","family":"Duffney","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-dong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona M.","family":"Rodriguiz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry H.","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology,"},{"name":"Department of Psychology and Neuroscience,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-7278","authenticated-orcid":true,"given":"Richard J.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-3688","authenticated-orcid":true,"given":"Ru-Rong","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurobiology,"},{"name":"Cellular and Molecular Biology Program,"},{"name":"Department of Anesthesiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Wetsel","sequence":"additional","affiliation":[{"name":"Department of Neurobiology,"},{"name":"Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA."},{"name":"Department of Cell Biology,"},{"name":"Duke Institute of Brain Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology,"},{"name":"Cellular and Molecular Biology Program,"},{"name":"Department of Pediatrics,"},{"name":"Duke Institute of Brain Science, and"},{"name":"Genomics and Genetics Graduate Program, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2017,10,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.03.016"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1489"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.57"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.589"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004580"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.03.017"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22128"},{"issue":"4","key":"B8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/ajmg.b.32232","article-title":"Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes","volume":"165B","author":"Noor","year":"2014","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.172"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906232107"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.24"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.07.009"},{"issue":"1","key":"B13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000339119","article-title":"Neuropsychopathology in 7 patients with the 22q13 deletion syndrome: presence of bipolar disorder and progressive loss of skills","volume":"3","author":"Denayer","year":"2012","journal-title":"Mol Syndromol"},{"key":"B14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2147\/NDT.S30506","article-title":"Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?","volume":"8","author":"Verhoeven","year":"2012","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8954"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4196"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3713"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.3389\/fpsyt.2015.00105","article-title":"Toward a deeper understanding of the genetics of bipolar disorder","volume":"6","author":"Kerner","year":"2015","journal-title":"Front Psychiatry"},{"issue":"1","key":"B19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00439-009-0703-0","article-title":"Genetics of psychosis; insights from views across the genome","volume":"126","author":"O\u2019Donovan","year":"2009","journal-title":"Hum Genet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.181"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2016.0251"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilu026"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2010.3"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.58"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2010.04.002"},{"issue":"7402","key":"B26","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nature11015","article-title":"Autistic-like behaviours and hyperactivity in mice lacking ProSAP1\/Shank2","volume":"486","author":"Schmeisser","year":"2012","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature11208"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.060749"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-4098-4"},{"key":"B30"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-2048-7"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/BF00428203"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2016.09.005"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2015.07.017"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.13020185"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12425"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nature12630"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-006-9093-4"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr470"},{"key":"B40"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.01.009"},{"issue":"3\u20134","key":"B42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<93::AID-GENE10>3.0.CO;2-W","article-title":"Cre recombinase expression in cerebellar Purkinje cells","volume":"28","author":"Barski","year":"2000","journal-title":"Genesis"},{"issue":"15","key":"B43","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002","article-title":"Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage","volume":"22","author":"Gorski","year":"2002","journal-title":"J Neurosci"},{"issue":"4","key":"B44","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1523\/JNEUROSCI.21-04-01211.2001","article-title":"Laminar organization of the NMDA receptor complex within the postsynaptic density","volume":"21","author":"Valtschanoff","year":"2001","journal-title":"J Neurosci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.119"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/ng1933"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002521"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2010.09091379"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2010.04.032"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.05.009"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2015.08.008"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.11.009"},{"key":"B53","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms12627","article-title":"Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice","volume":"7","author":"Peter","year":"2016","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1849-16.2016"},{"issue":"pt 1","key":"B55","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1042\/bj20031577","article-title":"Characterization of an ankyrin repeat-containing Shank2 isoform (Shank2E) in liver epithelial cells","volume":"380","author":"McWilliams","year":"2004","journal-title":"Biochem J"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.29510"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002521"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2014.13081008"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1080\/09540260902962107"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.01.003"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2011.00720.x"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.181"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.12.040"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1175-13.2013"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nature09965"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e3280117733"},{"key":"B67","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/7854_2010_49","article-title":"Strategies for the development of animal models for bipolar disorder: new opportunities and new challenges","volume":"5","author":"Einat","year":"2011","journal-title":"Curr Top Behav Neurosci"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01318.x"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1101\/gr.749203"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2005.08.003"},{"key":"B71","article-title":"Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism","volume":"7","author":"Wang","year":"2016","journal-title":"Nat Commun"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80596-6"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.74.1.181"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr212"},{"key":"B75"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/92052\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:32:31Z","timestamp":1779197551000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/92052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,19]]},"references-count":75,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2017,10,19]]},"published-print":{"date-parts":[[2017,10,19]]}},"alternative-id":["10.1172\/jci.insight.92052"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.92052","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,19]]},"article-number":"e92052"}}