Homozygous CHD8 mutation intensifies ASD phenotypes and attenuates sex differences
mice on the same hybrid background across brain volume, cerebral blood flow, neuronal firing, synaptic transmission, and transcriptome revealed a gene dosage-dependent attenuation of sexual dimorphic phenotypes that varied by developmental stage and brain region. Transcriptomic analyses further implicated pathways related to synaptic function, RNA splicing, and mitochondrial activity in mediating differences in male-female protection and susceptibility. Thus, a homozygous Chd8 mutation not only intensifies ASD-related traits but can also diminish typical sex-specific severity patterns, uncovering a novel link between mutation strength and sexual dimorphism in ASD.
Authors
- Hwajin Jung (ORCID: https://orcid.org/0000-0001-6194-9648)
- Jae‐Joong Kim (ORCID: https://orcid.org/0000-0002-2714-2282)
- Yong Gyu Kim (ORCID: https://orcid.org/0000-0002-4378-6248)
- Seongbin Kim (ORCID: https://orcid.org/0009-0000-1105-5558)
- Eunee Lee (ORCID: https://orcid.org/0000-0001-9726-4819)
- Seungjoon Lee (ORCID: https://orcid.org/0000-0002-8583-528X)
- Eunkyu Hwang (ORCID: https://orcid.org/0000-0002-8830-0512)
- Heon Yung Gee (ORCID: https://orcid.org/0000-0002-8741-6177)
- Soogeun Shin (ORCID: https://orcid.org/0009-0009-4227-9904)
- Sang‐Han Choi (ORCID: https://orcid.org/0000-0002-4622-3651)
- Sooyeon Lee (ORCID: https://orcid.org/0000-0001-6244-4975)
- Hyojin Kang (ORCID: https://orcid.org/0000-0002-3403-276X)
- Heera Moon
- Se Jin Kim (ORCID: https://orcid.org/0009-0006-5244-4887)
- Gina Lee
- Eunjoon Kim (ORCID: https://orcid.org/0000-0001-5518-6584)
- Chanhee Lee
- Seong-Gi Kim (ORCID: https://orcid.org/0000-0003-1960-4464)
Institutions
- Korea Advanced Institute of Science and Technology (KR)
- Yonsei University (KR)
- Institute for Basic Science (KR)
- Yonsei University Health System (KR)
- Sungkyunkwan University (KR)
- Korea Institute of Science & Technology Information (KR)
Publication Details
- Journal
- Molecular Psychiatry
- Published
- 2026-05-09
- DOI
- https://doi.org/10.1038/s41380-026-03646-9
- Primary Topic
- Autism Spectrum Disorder Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00