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Adv."],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:p>\n                    Loss-of-function mutations in genes encoding lysine demethylases specific for trimethylated lysine 4 of histone 3 (H3K4me3) are associated with neurodevelopmental conditions, including autism spectrum disorder (ASD) and intellectual disability (ID). To study the role of KDM5B (lysine demethylase 5B)\u2013mediated H3K4me3 demethylation, we investigated neurodevelopmental phenotypes in mice without KDM5B demethylase activity. These mice exhibited autism-like behaviors and increased brain size. H3K4me3 levels and the expression of neurodevelopmental genes were increased in the developing\n                    <jats:italic toggle=\"yes\">Kdm5b<\/jats:italic>\n                    mutant neocortex. Increased H3K4me3 levels at the promoter and associated expression of the\n                    <jats:italic toggle=\"yes\">Grin2d<\/jats:italic>\n                    gene were associated with increased levels of\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate receptor subunit 2D (NMDAR2D) protein in synaptosomes isolated from the early postnatal\n                    <jats:italic toggle=\"yes\">Kdm5b<\/jats:italic>\n                    -deficient neocortex. Treating mice with the NMDAR antagonist memantine rescued deficits in ultrasonic vocalizations. These findings suggest that increased H3K4me3 levels and associated\n                    <jats:italic toggle=\"yes\">Grin2d<\/jats:italic>\n                    gene up-regulation disrupt brain development and function, leading to socio-communication deficits and identify a potential therapeutic target for neurodevelopmental disorders associated with KDM5B deficiency.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adq6577","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:00:40Z","timestamp":1779300040000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9682-9811","authenticated-orcid":true,"given":"Leticia","family":"P\u00e9rez-Sisqu\u00e9s","sequence":"first","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Guy\u2019s Hospital, King\u2019s College London, London SE1 9RT, UK."},{"name":"MRC Centre for Neurodevelopmental Disorders, New Hunt\u2019s House, King\u2019s College London, London SE1 1UL, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-133X","authenticated-orcid":true,"given":"Shail U.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Guy\u2019s Hospital, King\u2019s College London, London SE1 9RT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Caruso","sequence":"additional","affiliation":[{"name":"Research Coordination and Support Service, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-7355","authenticated-orcid":true,"given":"Josephine L.","family":"Robb","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Sciences, University of Exeter Medical School, Hatherly Laboratories, Prince of Wales Road, Exeter EX4 4PS, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex P. 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