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Heterozygous inherited mutations in their principle subunits K<jats:sub>v<\/jats:sub>7.2\/KCNQ2 and K<jats:sub>v<\/jats:sub>7.3\/KCNQ3 cause benign familial neonatal epilepsy whereas patients with de novo heterozygous K<jats:sub>v<\/jats:sub>7.2 mutations are associated with early\u2010onset epileptic encephalopathy and neurodevelopmental disorders characterized by intellectual disability, developmental delay and autism. However, the role of K<jats:sub>v<\/jats:sub>7.2\u2010containing K<jats:sub>v<\/jats:sub>7 channels in behaviors especially autism\u2010associated behaviors has not been described. Because pathogenic K<jats:sub>v<\/jats:sub>7.2 mutations in patients are typically heterozygous loss\u2010of\u2010function mutations, we investigated the contributions of K<jats:sub>v<\/jats:sub>7.2 to exploratory, social, repetitive and compulsive\u2010like behaviors by behavioral phenotyping of both male and female<jats:italic>KCNQ2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice that were heterozygous null for the<jats:italic>KCNQ2<\/jats:italic>gene. Compared with their wild\u2010type littermates, male and female<jats:italic>KCNQ2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice displayed increased locomotor activity in their home cage during the light phase but not the dark phase and showed no difference in motor coordination, suggesting hyperactivity during the inactive light phase. In the dark phase,<jats:italic>KCNQ2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>group showed enhanced exploratory behaviors, and repetitive grooming but decreased sociability with sex differences in the degree of these behaviors. While male<jats:italic>KCNQ2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice displayed enhanced compulsive\u2010like behavior and social dominance, female<jats:italic>KCNQ2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice did not. In addition to elevated seizure susceptibility, our findings together indicate that heterozygous loss of K<jats:sub>v<\/jats:sub>7.2 induces behavioral abnormalities including autism\u2010associated behaviors such as reduced sociability and enhanced repetitive behaviors. Therefore, our study is the first to provide a tangible link between loss\u2010of\u2010function K<jats:sub>v<\/jats:sub>7.2 mutations and the behavioral comorbidities of K<jats:sub>v<\/jats:sub>7.2\u2010associated epilepsy.<\/jats:p>","DOI":"10.1111\/gbb.12599","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T16:09:40Z","timestamp":1562602180000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Heterozygous loss of epilepsy gene<i>KCNQ2<\/i>alters social, repetitive and exploratory behaviors"],"prefix":"10.1111","volume":"19","author":[{"given":"Eung Chang","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Illinois at Urbana\u2010Champaign Urbana Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimin","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of 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