Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes

Kensuke Matsumura, Kaoru Seiriki, Shota Okada, Masashi Nagase, Shinya Ayabe, Ikuko Yamada, Tamio Furuse, Hirotoshi Shibuya, Yuka Yasuda, Hidenaga Yamamori, Michiko Fujimoto, Kazuki Nagayasu, Kana Yamamoto, Kohei Kitagawa, Hiroki Miura, Nanaka Gotoda-Nishimura, Hisato Igarashi, Misuzu Hayashida, Masayuki Baba, Momoka Kondo, Shigeru Hasebe, Kosei Ueshima, Atsushi Kasai, Yukio Ago, Atsuko Hayata-Takano, Norihito Shintani, Tokuichi Iguchi, Makoto Sato, Shun Yamaguchi, Masaru Tamura, Shigeharu Wakana, Atsushi Yoshiki, Ayako M. Watabe, Hideyuki Okano, Kazuhiro Takuma, Ryota Hashimoto, Hitoshi Hashimoto () and Takanobu Nakazawa ()
Additional contact information
Kensuke Matsumura: Osaka University
Kaoru Seiriki: Osaka University
Shota Okada: Osaka University
Masashi Nagase: Jikei University School of Medicine
Shinya Ayabe: RIKEN BioResource Research Center
Ikuko Yamada: RIKEN BioResource Research Center
Tamio Furuse: RIKEN BioResource Research Center
Hirotoshi Shibuya: RIKEN BioResource Research Center
Yuka Yasuda: National Center of Neurology and Psychiatry
Hidenaga Yamamori: National Center of Neurology and Psychiatry
Michiko Fujimoto: National Center of Neurology and Psychiatry
Kazuki Nagayasu: Osaka University
Kana Yamamoto: Osaka University
Kohei Kitagawa: Osaka University
Hiroki Miura: Osaka University
Nanaka Gotoda-Nishimura: Osaka University
Hisato Igarashi: Osaka University
Misuzu Hayashida: Osaka University
Masayuki Baba: Osaka University
Momoka Kondo: Osaka University
Shigeru Hasebe: Osaka University
Kosei Ueshima: Osaka University
Atsushi Kasai: Osaka University
Yukio Ago: Osaka University
Atsuko Hayata-Takano: Osaka University
Norihito Shintani: Osaka University
Tokuichi Iguchi: Osaka University
Makoto Sato: Osaka University
Shun Yamaguchi: Gifu University Graduate School of Medicine
Masaru Tamura: RIKEN BioResource Research Center
Shigeharu Wakana: RIKEN BioResource Research Center
Atsushi Yoshiki: RIKEN BioResource Research Center
Ayako M. Watabe: Jikei University School of Medicine
Hideyuki Okano: Keio University School of Medicine
Kazuhiro Takuma: Osaka University
Ryota Hashimoto: National Center of Neurology and Psychiatry
Hitoshi Hashimoto: Osaka University
Takanobu Nakazawa: Osaka University

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14697-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14697-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14697-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().