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Title
Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice
Author(s)
정화진김은준강효진
Publication Year
2018-08-13
Abstract
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, includ- ing 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 associ- ated 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.
Keyword
CHD8; Autism; sexually dimorphic
Journal Title
Nature neuroscience
Citation Volume
21
ISSN
1097-6256
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Appears in Collections:
7. KISTI 연구성과 > 학술지 발표논문
URI
https://repository.kisti.re.kr/handle/10580/14795
http://www.ndsl.kr/ndsl/search/detail/article/articleSearchResultDetail.do?cn=NART90647971
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