{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:48:29Z","timestamp":1790286509703,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"crossref","award":["Independent Research Institutes Infrastructure Support Scheme"],"award-info":[{"award-number":["Independent Research Institutes Infrastructure Support Scheme"]}],"id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004752","name":"Victorian Government","doi-asserted-by":"crossref","award":["Operational Infrastructure Support Grant"],"award-info":[{"award-number":["Operational Infrastructure Support Grant"]}],"id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian National Health and Medical Research Council","award":["1160517,2010711,1081421,1176789,1194345,1154970"],"award-info":[{"award-number":["1160517,2010711,1081421,1176789,1194345,1154970"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:p>\n                    Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the\n                    <jats:italic>KAT6B<\/jats:italic>\n                    (\n                    <jats:italic>MYST4\/MORF\/QFK<\/jats:italic>\n                    ) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific\n                    <jats:italic>KAT6B<\/jats:italic>\n                    mutations and\n                    <jats:italic>Kat6b<\/jats:italic>\n                    heterozygous mice (\n                    <jats:italic>\n                      Kat6b\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation.\n                    <jats:italic>\n                      Kat6b\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyl-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of\n                    <jats:italic>\n                      Kat6b\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice and partially reversed gene expression changes in\n                    <jats:italic>\n                      Kat6b\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    cortical neurons. Both compounds improved sociability in\n                    <jats:italic>\n                      Kat6b\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1172\/jci167672","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T14:00:32Z","timestamp":1711893632000},"source":"Crossref","is-referenced-by-count":21,"title":["Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3322-9701","authenticated-orcid":true,"given":"Maria I.","family":"Bergamasco","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"Department of Medical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah K.","family":"Vanyai","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"Department of Medical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-8450","authenticated-orcid":true,"given":"Alexandra L.","family":"Garnham","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"Department of Medical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niall D.","family":"Geoghegan","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"Department of Medical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3505-2631","authenticated-orcid":true,"given":"Adam P.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Centre for Neurosciences of Speech, University of Melbourne, Parkville, Victoria, Australia."},{"name":"Redenlab Inc., Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Eccles","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"Department of Medical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Rogers","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"Department of Medical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9221-2892","authenticated-orcid":true,"given":"Gordon K.","family":"Smyth","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia."},{"name":"School of Mathematics and Statistics, University of 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