{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T23:45:30Z","timestamp":1778111130914,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T00:00:00Z","timestamp":1566518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002069","name":"Fraternal Order of Eagles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Heterozygous mutations in <jats:italic>PTEN<\/jats:italic>, which encodes a negative regulator of the mTOR and \u03b2\u2010catenin signaling pathways, cause macrocephaly\/autism syndrome. However, the neurobiological substrates of the core symptoms of this syndrome are poorly understood. Here, we investigate the relationship between cerebral cortical overgrowth and social behavior deficits in conditional <jats:italic>Pten<\/jats:italic> heterozygous female mice (<jats:italic>Pten<\/jats:italic> cHet) using Emx1\u2010Cre, which is expressed in cortical pyramidal neurons and a subset of glia. We found that conditional heterozygous mutation of <jats:italic>Ctnnb1<\/jats:italic> (encoding \u03b2\u2010catenin) suppresses <jats:italic>Pten<\/jats:italic> cHet cortical overgrowth, but not social behavioral deficits, whereas conditional heterozygous mutation of <jats:italic>Mtor<\/jats:italic> suppresses social behavioral deficits, but not cortical overgrowth. Neuronal activity in response to social cues and excitatory synapse markers are elevated in the medial prefrontal cortex (mPFC) of <jats:italic>Pten<\/jats:italic> cHet mice, and heterozygous mutation in <jats:italic>Mtor<\/jats:italic>, but not <jats:italic>Ctnnb1<\/jats:italic>, rescues these phenotypes. These findings indicate that macroscale cerebral cortical overgrowth and social behavioral phenotypes caused by <jats:italic>Pten<\/jats:italic> haploinsufficiency can be dissociated based on responsiveness to genetic suppression of <jats:italic>Ctnnb1<\/jats:italic> or <jats:italic>Mtor<\/jats:italic>. Furthermore, neuronal connectivity appears to be one potential substrate for mTOR\u2010mediated suppression of social behavioral deficits in <jats:italic>Pten<\/jats:italic> haploinsufficient mice. <jats:italic><jats:bold>Autism Res<\/jats:bold> 2019, 12: 1463\u20131471<\/jats:italic>. \u00a9 2019 International Society for Autism Research, Wiley Periodicals, Inc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>A subgroup of individuals with autism display overgrowth of the head and the brain during development. Using a mouse model of an autism risk gene, <jats:italic>Pten<\/jats:italic>, that displays both brain overgrowth and social behavioral deficits, we show here that that these two symptoms can be dissociated. Reversal of social behavioral deficits in this model is associated with rescue of abnormal synaptic markers and neuronal activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/aur.2186","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T07:35:42Z","timestamp":1566545742000},"page":"1463-1471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic Suppression of mTOR Rescues Synaptic and Social Behavioral Abnormalities in a Mouse Model of <i>Pten<\/i> Haploinsufficiency"],"prefix":"10.1002","volume":"12","author":[{"given":"Wen\u2010Chin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neuroscience The Scripps Research Institute  Jupiter Florida"},{"name":"The Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute  San Diego 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