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Recently, several genome\u2010wide association studies have implicated DGK<\/jats:styled-content><\/jats:italic>\u03b7 in the etiology of bipolar disorder (BPD<\/jats:styled-content>). However, it is still unknown whether DGK<\/jats:styled-content>\u03b7 is indeed related to BPD<\/jats:styled-content>. In this study, we generated DGK<\/jats:styled-content>\u03b7\u2010knockout (KO<\/jats:styled-content>) mice and performed behavioral tests such as the open field test, the elevated plus maze test and tail suspension test using the KO<\/jats:styled-content> mice to investigate the effects of DGK<\/jats:styled-content>\u03b7 deficits on psychomotor behavior. Intriguingly, DGK<\/jats:styled-content>\u03b7\u2010KO<\/jats:styled-content> mice displayed an overall behavioral profile that is similar to human mania, including hyperactivity, less anxiety and less depression\u2010like behavior. In addition, these phenotypes were significantly attenuated by the administration of a BPD<\/jats:styled-content> (mania) remedy, namely, lithium. Moreover, DGK<\/jats:styled-content>\u03b7\u2010KO<\/jats:styled-content> mice showed impairment in glycogen synthase kinase (GSK<\/jats:styled-content>) 3\u03b2 signaling, which is closely related to BPD<\/jats:styled-content>. These findings clearly support the linkage between BPD<\/jats:styled-content> and DGK<\/jats:styled-content>\u03b7 that is implicated by genome\u2010wide association studies. Moreover, this study provides DGK<\/jats:styled-content>\u03b7\u2010KO<\/jats:styled-content> mice as a previously unrecognized model that reflects several features of human BPD<\/jats:styled-content> with manic episodes and revealed an important role for DGK<\/jats:styled-content>\u03b7 in regulating behavior and mood through, at least in part, GSK<\/jats:styled-content>3\u03b2 signaling.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nSeveral genome\u2010wide association studies have implicated diacylglycerol kinase (DGK) \u03b7 gene in the etiology of bipolar disorder (BPD). In this study, we revealed that DGK\u03b7\u2010knockout (KO) mice displayed an overall behavioral profile that is similar to mania of BPD and is lithium (BPD (mania) remedy)\u2010sensitive. DGK\u03b7 may regulate behavior and mood through, at least in part, glycogen synthase kinase (GSK) 3\u03b2 signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13661","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T18:10:15Z","timestamp":1462990215000},"page":"448-456","source":"Crossref","is-referenced-by-count":35,"title":["Deficiency of diacylglycerol kinase \u03b7 induces lithium\u2010sensitive mania\u2010like behavior"],"prefix":"10.1111","volume":"138","author":[{"given":"Takeshi","family":"Isozaki","sequence":"first","affiliation":[{"name":"Department of Chemistry Graduate School of Science Chiba University Inage\u2010ku Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Komenoi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Graduate School of Science Chiba University Inage\u2010ku Chiba 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