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In the present study we sought to investigate interactions between two distinct point mutations in the mouse<jats:italic>Disc1<\/jats:italic>gene (L100P and Q31L) and maternal immune activation (MIA) during pregnancy with polyinosinic:polycytidylic acid (polyI:C). PolyI:C given at 5 mg\/kg impaired cognitive and social behavior in both wild-type (WT) and<jats:italic>Disc1<\/jats:italic>-Q31L<jats:sup>+\/\u2212<\/jats:sup>offspring, and reduced prepulse inhibition at 16 but not 8 weeks of age.<jats:italic>Disc1<\/jats:italic>-L100P<jats:sup>+\/\u2212<\/jats:sup>mutants were more sensitive to MIA than WT or Disc1-Q31L<jats:sup>+\/\u2212<\/jats:sup>mice. Interleukin-6 (IL-6) is a critical cytokine for mediating the behavioral and transcriptional effects of polyI:C. We found a more pronounced increase of IL-6 in response to polyI:C in fetal brain in<jats:italic>Disc1<\/jats:italic>-L100P<jats:sup>+\/\u2212<\/jats:sup>mice compared with WT or<jats:italic>Disc1<\/jats:italic>-Q31L<jats:sup>+\/\u2212<\/jats:sup>mice. Coadministration of an anti-IL-6 antibody with polyI:C reversed schizophrenia-related behavioral phenotypes in<jats:italic>Disc1<\/jats:italic>-L100P<jats:sup>+\/\u2212<\/jats:sup>mice. In summary, we found specific interactions between discrete genetic (<jats:italic>Disc1<\/jats:italic>-L100P<jats:sup>+\/\u2212<\/jats:sup>) and environmental factors (MIA) that exacerbate schizophrenia-related phenotypes. IL-6 may be important in the pathophysiology of this interaction.<\/jats:p>","DOI":"10.1523\/jneurosci.0091-13.2013","type":"journal-article","created":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T18:33:21Z","timestamp":1367433201000},"page":"7654-7666","source":"Crossref","is-referenced-by-count":141,"title":["Maternal Immune Activation during Gestation Interacts with<i>Disc1<\/i>Point Mutation to Exacerbate Schizophrenia-Related Behaviors in Mice"],"prefix":"10.1523","volume":"33","author":[{"given":"Tatiana V.","family":"Lipina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clement","family":"Zai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Hlousek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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