Postnatal age-differential ASD-like transcriptomic, synaptic, and behavioral deficits in Myt1l-mutant mice

Seongbin Kim, Hyoseon Oh, Sang Han Choi, Ye Eun Yoo, Young Woo Noh, Yisul Cho, Geun Ho Im, Chanhee Lee, Yusang Oh, Esther Yang, Gyuri Kim, Won Suk Chung, Hyun Kim, Hyojin Kang, Yongchul Bae, Seong Gi Kim, Eunjoon Kim

Research output: Contribution to journalArticlepeer-review

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 Myt1l-heterozygous mutant (Myt1l-HT) mice display postnatal age-differential ASD-related phenotypes: newborn Myt1l-HT mice, with strong Myt1l 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 Myt1l 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, Myt1l 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 Myt1l expression in juveniles.

Original languageEnglish
Article number111398
JournalCell Reports
Volume40
Issue number12
DOIs
Publication statusPublished - 2022 Sep 20

Keywords

  • autism spectrum disorder
  • CP: Neuroscience
  • intellectual disability
  • neurodevelopmental disorder
  • neuronal differentiation
  • schizophrenia
  • social and repetitive behaviors
  • synaptic transmission
  • transcription factor
  • transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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