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Publication : Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice.

First Author  Jung H Year  2018
Journal  Nat Neurosci Volume  21
Issue  9 Pages  1218-1228
PubMed ID  30104731 Mgi Jnum  J:267025
Mgi Id  MGI:6257168 Doi  10.1038/s41593-018-0208-z
Citation  Jung H, et al. (2018) Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice. Nat Neurosci 21(9):1218-1228
abstractText  Autism spectrum disorders (ASDs) are four times more common in males than in females, but the underlying mechanisms are poorly understood. We characterized sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8 (Chd8(+/N2373K)) that was first identified in human CHD8 (Asn2373LysfsX2), a strong ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant mice displayed a range of abnormal behaviors during pup, juvenile, and adult stages, including enhanced mother-seeking ultrasonic vocalization, enhanced attachment to reunited mothers, and isolation-induced self-grooming, their female counterparts do not. This behavioral divergence was associated with sexually dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic profiles. Specifically, female mice displayed suppressed baseline neuronal excitation, enhanced inhibitory synaptic transmission and neuronal firing, and increased expression of genes associated with extracellular vesicles and the extracellular matrix. Our results suggest that a human CHD8 mutation leads to sexually dimorphic changes ranging from transcription to behavior in mice.
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