{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:17:53Z","timestamp":1773389873483,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merit Review Award","award":["I01BX003195"],"award-info":[{"award-number":["I01BX003195"]}]},{"name":"U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development Service (to JOC) and the National Center for Advancing Translational Studies","award":["UL1TR001120"],"award-info":[{"award-number":["UL1TR001120"]}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil","doi-asserted-by":"crossref","award":["T32 HL007446"],"award-info":[{"award-number":["T32 HL007446"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism Spectrum Disorder (ASD) is a developmental disorder that manifests a broad variability of phenotypes. The underlying factors contributing to the diverse presentation of autistic phenotypes remain poorly understood. Studies have shown that environmental and genetic factors could contribute to ASD. Additionally, there is a sex bias in the disorder, where the prevalence in males is higher than in females. But it is still unknown how exposure to similar risk factors can lead to different phenotypes. The three-hit theory states that the vulnerability of an individual to develop ASD is modulated by the interplay between genetic predisposition, sex, and environmental insults. To better understand this phenomenon, we investigated whether an environmental insult, via maternal immune activation (MIA) during pregnancy could influence the development of the autistic-like phenotype in a genetically predisposed mouse strain, contactin-associated protein-like 2 (CNTNAP2) knockout. CNTNAP2 knockout, sex, and maternal immune activation had significantly additive effects on repetitive\/stereotyped and social behavior in the offspring, while working memory and sensory gating were not affected by hits. These results indicate that genetics, sex, and environment interact to influence autistic-like phenotypes in a behavior-specific manner.<\/jats:p>","DOI":"10.3390\/ijms27062566","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:43:27Z","timestamp":1773225807000},"page":"2566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Gene, Environment, and Sex Interaction in the Development of Autistic-like Phenotype in Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3784-2036","authenticated-orcid":false,"given":"Danielle","family":"Santana-Coelho","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA"},{"name":"South Texas Veterans Health System, Audie L. Murphy VA Hospital, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-3813","authenticated-orcid":false,"given":"Grace","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA"},{"name":"South Texas Veterans Health System, Audie L. Murphy VA Hospital, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA"},{"name":"South Texas Veterans Health System, Audie L. Murphy VA Hospital, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason C.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA"},{"name":"South Texas Veterans Health System, Audie L. Murphy VA Hospital, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/cercor\/bhx022","article-title":"Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity","volume":"28","author":"Liska","year":"2017","journal-title":"Cereb. 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