Oligodendrocyte dysfunction due to Chd8 mutation gives rise to behavioral deficits in mice

Atsuki Kawamura, Yuta Katayama, Masaaki Nishiyama, Hirotaka Shoji, Kota Tokuoka, Yoshifumi Ueta, Mariko Miyata, Tadashi Isa, Tsuyoshi Miyakawa, Akiko Hayashi-Takagi, Keiichi I. Nakayama

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Mutations in the gene encoding the chromatin remodeler CHD8 are strongly associated with autism spectrum disorder (ASD). CHD8 haploinsufficiency also results in autistic phenotypes in humans and mice. Although myelination defects have been observed in individuals with ASD, whether oligodendrocyte dysfunction is responsible for autistic phenotypes has remained unknown. Here we show that reduced expression of CHD8 in oligodendrocytes gives rise to abnormal behavioral phenotypes in mice. CHD8 was found to regulate the expression of many myelination-related genes and to be required for oligodendrocyte maturation and myelination. Ablation of Chd8 specifically in oligodendrocytes of mice impaired myelination, slowed action potential propagation and resulted in behavioral deficits including increased social interaction and anxiety-like behavior, with similar effects being apparent in Chd8 heterozygous mutant mice. Our results thus indicate that CHD8 is essential for myelination and that dysfunction of oligodendrocytes as a result of CHD8 haploinsufficiency gives rise to several neuropsychiatric phenotypes.

Original languageEnglish
Pages (from-to)1274-1291
Number of pages18
JournalHuman molecular genetics
Issue number8
Publication statusPublished - May 28 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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