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Although gene-environment interactions may explain the heterogeneous etiology of ASD, it is still largely unknown how the gene-environment interaction affects behavioral symptoms and pathophysiology in ASD. To address these questions, we used <jats:italic>Cntnap2<\/jats:italic> knockout mice (genetic factor, G) exposed to valproic acid during embryonic development (environmental factor, E) as a gene-environment interaction (G\u2009\u00d7\u2009E) model. Paradoxically, the social deficits observed in the respective G and E models were improved in the G\u2009\u00d7\u2009E model; however, the high seizure susceptibility was more severe in the G\u2009\u00d7\u2009E -model than in the G and E models. Repetitive self-grooming and hyperactivity did not differ among the three models. The amplitudes of miniature excitatory postsynaptic currents in layer 2\/3 pyramidal neurons of the medial prefrontal cortex were aberrant and similar in the G\u2009\u00d7\u2009E model when compared to the control group. Our findings suggest that the interaction of two risk factors does not always aggravate ASD symptoms but can also alleviate them, which may be key to understanding individual differences in behavioral phenotypes and symptom intensity.<\/jats:p>","DOI":"10.1038\/s41598-019-47680-w","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T10:02:56Z","timestamp":1565172176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Gene-environment interaction counterbalances social impairment in mouse models of autism"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-0592","authenticated-orcid":false,"given":"Ji-Woon","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwanghoon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri Jin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson Luck","family":"Gonzales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ah","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Seung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mee Jung","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hoon","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3104-2399","authenticated-orcid":false,"given":"ChiHye","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1764-6740","authenticated-orcid":false,"given":"Chan Young","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,7]]},"reference":[{"key":"47680_CR1","unstructured":"APA. 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