Postnatal age-differential ASD-like transcriptomic, synaptic, and behavioral deficits in Myt1l-mutant miceopen access
- Authors
- Kim, Seongbin; Oh, Hyoseon; Choi, Sang Han; Yoo, Ye-Eun; Noh, Young Woo; Cho, Yisul; Im, Geun Ho; Lee, Chanhee; Oh, Yusang; Yang, Esther; Kim, Gyuri; Chung, Won-Suk; Kim, Hyun; Kang, Hyojin; Bae, Yongchul; Kim, Seong-Gi; Kim, Eunjoon
- Issue Date
- Sep-2022
- Publisher
- Cell Press
- Keywords
- autism spectrum disorder; CP: Neuroscience; intellectual disability; neurodevelopmental disorder; neuronal differentiation; schizophrenia; social and repetitive behaviors; synaptic transmission; transcription factor; transcriptome
- Citation
- Cell Reports, v.40, no.12
- Indexed
- SCIE
SCOPUS
- Journal Title
- Cell Reports
- Volume
- 40
- Number
- 12
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61699
- DOI
- 10.1016/j.celrep.2022.111398
- ISSN
- 2211-1247
2211-1247
- Abstract
- Myelin transcription factor 1 like (Myt1l), a zinc-finger transcription factor, promotes neuronal differentiation and is implicated in autism spectrum disorder (ASD) and intellectual disability. However, it remains unclear whether Myt1l promotes neuronal differentiation in vivo and its deficiency in mice leads to disease-related phenotypes. Here, we report that Mythl-heterozygous mutant (Myt1l-HT) mice display postnatal age-differential ASD-related phenotypes: newborn Myt1l-HT mice, with strong Mythl expression, show ASD-like transcriptomic changes involving decreased synaptic gene expression and prefrontal excitatory synaptic transmission and altered righting reflex. Juvenile Myt1l-HT mice, with markedly decreased Mythl expression, display reverse ASD-like transcriptomes, increased prefrontal excitatory transmission, and largely normal behaviors. Adult Myt1l-HT mice show ASD-like transcriptomes involving astrocytic and microglial gene upregulation, increased prefrontal inhibitory transmission, and behavioral deficits. Therefore, Mythl haploinsufficiency leads to ASD-related phenotypes in newborn mice, which are temporarily normalized in juveniles but re-appear in adults, pointing to continuing phenotypic changes long after a marked decrease of Mythl expression in juveniles.
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- Appears in
Collections - 1. Basic Science > Department of Anatomy > 1. Journal Articles
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