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Germline mutation in the tumor suppressor gene\n                      <jats:italic>PTEN<\/jats:italic>\n                      is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific\n                      <jats:italic>Pten<\/jats:italic>\n                      loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant\n                      <jats:italic>Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Y68H\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the\n                      <jats:italic>Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Y68H\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the\n                      <jats:italic>Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Y68H\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      cortex, which profiled gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in\n                      <jats:italic>Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Y68H\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0018), and oxytocin protein was strongly overexpressed in the\n                      <jats:italic>Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Y68H\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      hypothalamus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The nuclear-predominant\n                      <jats:italic>Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Y68H\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and\/or novel therapeutic modalities that could be explored in individuals with germline mutations in\n                      <jats:italic>PTEN<\/jats:italic>\n                      with ASD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13229-021-00448-4","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T05:03:13Z","timestamp":1622782993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity"],"prefix":"10.1186","volume":"12","author":[{"given":"Nick","family":"Sarn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stetson","family":"Thacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunpil","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-5145","authenticated-orcid":false,"given":"Charis","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"issue":"4","key":"448_CR1","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1136\/jmg.2004.024646","volume":"42","author":"M Butler","year":"2005","unstructured":"Butler M, Dasouki M, Zhou X, Talebizadeh Z, Brown M, Takahashi T, et al. 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