{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:27:22Z","timestamp":1777544842512,"version":"3.51.4"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN#178329"],"award-info":[{"award-number":["FRN#178329"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    ATR-X syndrome, caused by mutations in the\n                    <jats:italic>ATRX<\/jats:italic>\n                    gene, leads to intellectual disability and neurodevelopmental deficits, with previous mouse models implicating forebrain ATRX loss in cognitive impairment. However, the region-specific requirements of neuronal ATRX for cognitive function remain unclear. Here, we generated conditional knockout mice with predominant deletion of ATRX in hippocampal CA1 pyramidal neurons in both pure C57Bl\/6J and hybrid C57Bl\/6J\u2009+\u2009129S2\/Sv genetic backgrounds. Immunofluorescence confirmed efficient ATRX loss in CA1 neurons, with mosaic expression throughout other forebrain structures. Behavioral analyses revealed that T29-1 CaMKII\u03b1-Cre ATRX knockout mice exhibited significant hypoactivity and increased anxiety traits, particularly in the open field, but retained normal hippocampal-dependent contextual fear memory and spatial learning and memory. In contrast, we confirmed that mice with robust forebrain-wide ATRX ablation in excitatory neurons (R1ag#5 CaMKII\u03b1-Cre-mediated) displayed deficits in these cognitive domains. Our findings demonstrate that ATRX-related intellectual disability requires disruption of broader hippocampal or forebrain circuits to elicit cognitive impairments in learning and memory.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0347770","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:31:23Z","timestamp":1777397483000},"page":"e0347770","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["ATRX function beyond hippocampal CA1 is required for cognitive deficits in mouse models of intellectual disability"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9559-2629","authenticated-orcid":true,"given":"Julia T.","family":"Brott","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-8715","authenticated-orcid":true,"given":"Nathalie G.","family":"B\u00e9rub\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"issue":"6","key":"pone.0347770.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/0092-8674(95)90287-2","article-title":"Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome)","volume":"80","author":"RJ Gibbons","year":"1995","journal-title":"Cell"},{"key":"pone.0347770.ref002"},{"key":"pone.0347770.ref003"},{"issue":"3","key":"pone.0347770.ref004","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1101\/gr.101477.109","article-title":"ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells","volume":"20","author":"LH Wong","year":"2010","journal-title":"Genome 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