KAT6B overexpression in mice causes aggression, anxiety, and epilepsy

Bergamasco, MI; Ozturk, E; Casillas-Espinosa, PM; Garnham, AL; Abeysekera, W; Wimmer, VC; Rajasekhar, P; Vanyai, HK; Whitehead, L; Blewitt, ME; Rogers, K; Vogel, AP; Hannan, AJ; Smyth, GK; Jones, NC; Thomas, T; Voss, AK

Author(s): Bergamasco, MI; Ozturk, E; Casillas-Espinosa, PM; Garnham, AL; Abeysekera, W; Wimmer, VC; Rajasekhar, P; Vanyai, HK; Whitehead, L; Blewitt, ME; Rogers, K; Vogel, AP; Hannan, AJ; Smyth, GK; Jones, NC; Thomas, T; Voss, AK;
Details: Publication Year 2025-03-21,Volume 28,Issue #3,Page 111953
Journal Title: iScience
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 KAT6B gene cause two cognitive disorders, Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS; OMIM:603736) and genitopatellar syndrome (GTPTS; OMIM:606170). Although the effects of KAT6B 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 Kat6b gene in mice caused aggression, anxiety, and spontaneous epilepsy. Kat6b overexpression led to an increase in histone H3 lysine 9 acetylation and upregulation of genes driving nervous system development and neuronal differentiation. Kat6b overexpression additionally promoted neural stem cell proliferation and favored neuronal over astrocyte differentiation in vivo and in vitro. Our results suggest that, in addition to loss-of-function alleles, gain-of-function KAT6B alleles may be detrimental for brain development.
Publisher: Elsevier
Keywords: Behavioral neuroscience; Biological sciences; Molecular neuroscience; Neuroscience
Research Division(s): Genetics and Gene Regulation; Personalised Oncology; Advanced Technology and Biology; Bioinformatics and Computational Biology
PubMed ID: 40083716
Publisher's Version: https://doi.org/10.1016/j.isci.2025.111953
Open Access at Publisher's Site: https://doi.org/10.1016/j.isci.2025.111953
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-03-19 09:29:36

Last Modified: 2025-04-08 03:12:58