{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:35:43Z","timestamp":1793172943588,"version":"4.5.0"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,4,3]]},"abstract":"<jats:p>\n                    Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (\n                    <jats:italic>SLC6A4<\/jats:italic>\n                    ) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT\n                    <jats:sub>1A<\/jats:sub>\n                    and 5HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1112345109","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T00:57:11Z","timestamp":1332205031000},"page":"5469-5474","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":296,"title":["Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior"],"prefix":"10.1073","volume":"109","author":[{"given":"Jeremy","family":"Veenstra-VanderWeele","sequence":"first","affiliation":[{"name":"Departments of aPsychiatry,"},{"name":"Pediatrics, and"},{"name":"Pharmacology,"},{"name":"Brain Institute, and"},{"name":"Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Muller","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Sauer","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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