Year: 2026
Type: article
Abstract: Mutations in the chromatin remodeler, CHD2 , are strongly associated with moderate to severe intellectual disability, autism and epilepsy, but the direct contribution of CHD2 mutations to clinical phenotypes is poorly understood. We report developmental and sex-specific behavioral changes in mice carrying a heterozygous mutation in Chd2 . Notably, Chd2 mutants display a range of abnormal behaviors including impairments in multiple forms of memory and social interaction. Memory impairments and memory-relevant transcriptional changes observed in Chd2 +/− mice are largely recapitulated in both sexes by conditional Chd2 +/− in adulthood. However, deficits in social behaviors and neuromodulatory system genes remain largely unaffected in conditional mutants. Reductions in interneuron density were identified throughout the brain of Chd2 +/− mice, and the GABA A positive allosteric modulator, L-838,417, was effective in treating abnormal social behavior. Our results suggest a postdevelopmental role for Chd2 in memory whereas neuropsychiatric conditions may be driven by more complex circuit mechanisms involving sexually dimorphic disruptions in brain development.
Source: Molecular Psychiatry
Authors: Sang Ho Yoon, Robert F. Hunt
Institution: University of California, Irvine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funder: National Institutes of Health
OpenAlex ID: W7140097818