{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["28(3)"],"submitter":["Bergamasco MI"],"funding":["Australian Government Department of Defence","The Chan Zuckerberg Initiative","National Health and Medical Research Council","Australian Government Department of Health and Aged Care","Lorenzo and Pamela Galli Charitable Trust"],"pubmed_abstract":["Loss of the gene encoding the histone acetyltransferase KAT6B (MYST4/MORF/QKF) causes developmental brain abnormalities as well as behavioral and cognitive defects in mice. In humans, heterozygous variants in the <i>KAT6B</i> gene cause two cognitive disorders, Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS; OMIM:603736) and genitopatellar syndrome (GTPTS; OMIM:606170). Although the effects of <i>KAT6B</i> homozygous and heterozygous mutations have been documented in humans and mice, KAT6B gain-of-function effects have not been reported. Here, we show that overexpression of the <i>Kat6b</i> gene in mice caused aggression, anxiety, and spontaneous epilepsy. <i>Kat6b</i> overexpression led to an increase in histone H3 lysine 9 acetylation and upregulation of genes driving nervous system development and neuronal differentiation. <i>Kat6b</i> overexpression additionally promoted neural stem cell proliferation and favored neuronal over astrocyte differentiation <i>in vivo</i> and <i>in vitro</i>. Our results suggest that, in addition to loss-of-function alleles, gain-of-function <i>KAT6B</i> alleles may be detrimental for brain development."],"journal":["iScience"],"pagination":["111953"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11904597"],"repository":["biostudies-literature"],"pubmed_title":["KAT6B overexpression in mice causes aggression, anxiety, and epilepsy."],"pmcid":["PMC11904597"],"pubmed_authors":["Smyth GK","Blewitt ME","Wimmer VC","Vogel AP","Ozturk E","Whitehead L","Bergamasco MI","Garnham AL","Abeysekera W","Rajasekhar P","Thomas T","Voss AK","Vanyai HK","Rogers K","Jones NC","Hannan AJ","Casillas-Espinosa PM"],"additional_accession":[]},"is_claimable":false,"name":"KAT6B overexpression in mice causes aggression, anxiety, and epilepsy.","description":"Loss of the gene encoding the histone acetyltransferase KAT6B (MYST4/MORF/QKF) causes developmental brain abnormalities as well as behavioral and cognitive defects in mice. In humans, heterozygous variants in the <i>KAT6B</i> gene cause two cognitive disorders, Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS; OMIM:603736) and genitopatellar syndrome (GTPTS; OMIM:606170). Although the effects of <i>KAT6B</i> homozygous and heterozygous mutations have been documented in humans and mice, KAT6B gain-of-function effects have not been reported. Here, we show that overexpression of the <i>Kat6b</i> gene in mice caused aggression, anxiety, and spontaneous epilepsy. <i>Kat6b</i> overexpression led to an increase in histone H3 lysine 9 acetylation and upregulation of genes driving nervous system development and neuronal differentiation. <i>Kat6b</i> overexpression additionally promoted neural stem cell proliferation and favored neuronal over astrocyte differentiation <i>in vivo</i> and <i>in vitro</i>. Our results suggest that, in addition to loss-of-function alleles, gain-of-function <i>KAT6B</i> alleles may be detrimental for brain development.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-02T21:11:24.914Z","creation":"2025-04-04T03:01:33.428Z"},"accession":"S-EPMC11904597","cross_references":{"pubmed":["40083716"],"doi":["10.1016/j.isci.2025.111953"]}}