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Almost every individual with\u00a0<jats:italic>SYNGAP1<\/jats:italic>\u2010related ID develops epilepsy, and approximately 50% have ASD. <jats:italic>SYNGAP1<\/jats:italic>\u2010related ID is estimated to account for at least 1% of ID cases. In mouse models with <jats:italic>Syngap1<\/jats:italic> mutations, strong cognitive and affective dysfunctions have been reported, yet some findings are inconsistent across studies. To further understand the behavioral significance of the <jats:italic>SYNGAP1<\/jats:italic> gene, we assessed various domains of behavior in <jats:italic>Syngap1<\/jats:italic> heterozygous mutant mice using a behavioral test battery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male mice with a heterozygous mutation in the <jats:italic>Syngap1<\/jats:italic> gene (<jats:italic>Syngap1<\/jats:italic><jats:sup>\u2212\/+<\/jats:sup> mice) created by Seth Grant's group were subjected to a battery of comprehensive behavioral tests, which examined general health, and neurological screens, rotarod, hot plate, open field, light\/dark transition, elevated plus maze, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, gait analysis, T\u2010maze, Y\u2010maze, Barnes maze, contextual and cued fear conditioning, and home cage locomotor activity. To control for type I errors due to multiple\u2010hypothesis testing, <jats:italic>P\u2010<\/jats:italic>values below the false discovery rate calculated by the Benjamini\u2010Hochberg method were considered as study\u2010wide statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Syngap1<\/jats:italic><jats:sup>\u2212\/+<\/jats:sup> mice showed increased locomotor activity, decreased prepulse inhibition, and impaired working and reference spatial memory, consistent with preceding studies. Impairment of context fear memory and increased startle reflex in <jats:italic>Syngap1<\/jats:italic> mutant mice could not be reproduced. Significant decreases in sensitivity to painful stimuli and impaired motor function were observed in <jats:italic>Syngap1<\/jats:italic><jats:sup>\u2212\/+<\/jats:sup> mice. Decreased anxiety\u2010like behavior and depression\u2010like behavior were noted, although increased locomotor activity is a potential confounding factor of these phenotypes. Increased home cage locomotor activity indicated hyperlocomotor activity not only in specific behavioral test conditions but also in familiar environments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In <jats:italic>Syngap1<\/jats:italic><jats:sup>\u2212\/+<\/jats:sup> mice, we could reproduce most of the previously reported cognitive and emotional deficits. The decreased sensitivity to painful stimuli and impaired motor function that we found in <jats:italic>Syngap1<\/jats:italic><jats:sup>\u2212\/+<\/jats:sup> mice are consistent with the common characteristics of patients with <jats:italic>SYNGAP<\/jats:italic>\u2010related ID. We further confirmed that the <jats:italic>Syngap1<\/jats:italic> heterozygote mouse recapitulates the symptoms of ID and ASD patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12073","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T17:34:56Z","timestamp":1563557696000},"page":"223-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Comprehensive behavioral analysis of heterozygous <i>Syngap1<\/i> knockout mice"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0024-4422","authenticated-orcid":false,"given":"Ryuichi","family":"Nakajima","sequence":"first","affiliation":[{"name":"Division of Systems Medical Science, Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4734-3583","authenticated-orcid":false,"given":"Keizo","family":"Takao","sequence":"additional","affiliation":[{"name":"Division of Animal Resources and Development, Life Science Research Center University of Toyama Toyama Japan"},{"name":"Section of Behavior Patterns, Center for Genetic Analysis of Behavior National Institute for Physiological Sciences Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-6454","authenticated-orcid":false,"given":"Satoko","family":"Hattori","sequence":"additional","affiliation":[{"name":"Division of Systems Medical Science, Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-6949","authenticated-orcid":false,"given":"Hirotaka","family":"Shoji","sequence":"additional","affiliation":[{"name":"Division of Systems Medical Science, Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9960-3597","authenticated-orcid":false,"given":"Noboru H.","family":"Komiyama","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, The Patrick Wild Centre for Research into Autism, Fragile X Syndrome &amp; Intellectual Disabilities The University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-8735","authenticated-orcid":false,"given":"Seth G. 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