{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:56:56Z","timestamp":1782863816293,"version":"3.54.5"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Oligodendrocytes (OLs) and myelination contribute to higher-order cognitive functions, and are impaired in several mental disorders, including schizophrenia (SZ). The SZ risk gene\n                      <jats:italic>transcription factor 4<\/jats:italic>\n                      (\n                      <jats:italic>TCF4<\/jats:italic>\n                      ) and\n                      <jats:italic>OLIG2<\/jats:italic>\n                      are two critical regulators of differentiation and maturation of oligodendrocyte precursor cells (OPCs) and OLs.\n                      <jats:italic>Tcf4<\/jats:italic>\n                      -\n                      <jats:italic>Olig2<\/jats:italic>\n                      double heterozygous deletion (\n                      <jats:italic>Tcf4<\/jats:italic>\n                      -\n                      <jats:italic>Olig2<\/jats:italic>\n                      dHet) mice have been shown to exhibit impairments in OL differentiation and myelination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Therefore, we performed a comprehensive behavioral profiling using a Research Domain Criterion (RDoC)-based pipeline in this model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Tcf4<\/jats:italic>\n                      -\n                      <jats:italic>Olig2<\/jats:italic>\n                      dHet mice showed impaired place learning in the positive valence system, reduced anxiety-like behaviors in the negative valence system, impaired remote fear memory in the cognitive domain, and abnormal sensorimotor gating.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Thus, subtle OLs and myelination impairments in\n                      <jats:italic>Tcf4<\/jats:italic>\n                      -\n                      <jats:italic>Olig2<\/jats:italic>\n                      dHet mice led to several psychiatric disorder-related behavioral deficits. We conclude that\n                      <jats:italic>Tcf4<\/jats:italic>\n                      -\n                      <jats:italic>Olig2<\/jats:italic>\n                      dHet mice represent a preclinical mouse model to study myelination-related mechanisms relevant for mental disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2026.1837159","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:12:07Z","timestamp":1782861127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mice lacking two alleles of the schizophrenia risk gene Tcf4 and Olig2 display deficits in anxiety-related behavior, sensorimotor gating, and cognition"],"prefix":"10.3389","volume":"20","author":[{"given":"Man-Hsin","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Molecular and Behavioral Neurobiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"International Max Planck Research School for Translational Psychiatry (IMPRS-TP)","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Molecular and Behavioral Neurobiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Stephan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Molecular and Behavioral Neurobiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"Systasy Bioscience GmbH","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Molecular and Behavioral Neurobiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Falkai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Molecular and Behavioral Neurobiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"Department of Clinical Translation, Max Planck Institute of Psychiatry","place":["Munich, Germany"]},{"name":"German Center for Mental Health (DZPG), Partner Site Munich\/Augsburg","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz J.","family":"Rossner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Molecular and Behavioral Neurobiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1538\/expanim.60.111","article-title":"Strain and sex differences in anxiety-like and social behaviors in C57BL\/6J and BALB\/cJ mice","volume":"60","author":"An","year":"2011","journal-title":"Exp. 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