Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

Soo Yeon Lee; Hanseul Kweon; Hyojin Kang; Eunjoon Kim

doi:10.3389/fnmol.2023.1111388

Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

Front Mol Neurosci. 2023 Feb 16:16:1111388. doi: 10.3389/fnmol.2023.1111388. eCollection 2023.

Authors

Soo Yeon Lee¹, Hanseul Kweon², Hyojin Kang³, Eunjoon Kim^{1

2}

Affiliations

¹ Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, Republic of Korea.
² Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
³ Division of National Supercomputing, Korea Institute of Science and Technology Information, Daejeon, Republic of Korea.

Abstract

Chd8^+/N2373K mice with a human C-terminal-truncating mutation (N2373K) display autistic-like behaviors in juvenile and adult males but not in females. In contrast, Chd8^+/S62X mice with a human N-terminal-truncating mutation (S62X) display behavioral deficits in juvenile males (not females) and adult males and females, indicative of age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8^+/S62X juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8^+/S62X males but in newborn and adult (not juvenile) Chd8^+/S62X females. These results point to age-differential sexual dimorphisms in Chd8^+/S62X mice at synaptic and transcriptomic levels, in addition to the behavioral level.

Keywords: age dependence; autism spectrum disorder; chromatin remodeling; sexual dimorphism; synapse; transcriptome.