論文

査読有り 筆頭著者 責任著者 国際誌
2021年3月3日

Cooperation of LIM domain-binding 2 (LDB2) with EGR in the pathogenesis of schizophrenia.

EMBO molecular medicine
  • Tetsuo Ohnishi
  • Yuji Kiyama
  • Fumiko Arima-Yoshida
  • Mitsutaka Kadota
  • Tomoe Ichikawa
  • Kazuyuki Yamada
  • Akiko Watanabe
  • Hisako Ohba
  • Kaori Tanaka
  • Akihiro Nakaya
  • Yasue Horiuchi
  • Yoshimi Iwayama
  • Manabu Toyoshima
  • Itone Ogawa
  • Chie Shimamoto-Mitsuyama
  • Motoko Maekawa
  • Shabeesh Balan
  • Makoto Arai
  • Mitsuhiro Miyashita
  • Kazuya Toriumi
  • Yayoi Nozaki
  • Rumi Kurokawa
  • Kazuhiro Suzuki
  • Akane Yoshikawa
  • Tomoko Toyota
  • Toshihiko Hosoya
  • Hiroyuki Okuno
  • Haruhiko Bito
  • Masanari Itokawa
  • Shigehiro Kuraku
  • Toshiya Manabe
  • Takeo Yoshikawa
  • 全て表示

13
4
開始ページ
e12574
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.15252/emmm.202012574

Genomic defects with large effect size can help elucidate unknown pathologic architecture of mental disorders. We previously reported on a patient with schizophrenia and a balanced translocation between chromosomes 4 and 13 and found that the breakpoint within chromosome 4 is located near the LDB2 gene. We show here that Ldb2 knockout (KO) mice displayed multiple deficits relevant to mental disorders. In particular, Ldb2 KO mice exhibited deficits in the fear-conditioning paradigm. Analysis of the amygdala suggested that dysregulation of synaptic activities controlled by the immediate early gene Arc is involved in the phenotypes. We show that LDB2 forms protein complexes with known transcription factors. Consistently, ChIP-seq analyses indicated that LDB2 binds to > 10,000 genomic sites in human neurospheres. We found that many of those sites, including the promoter region of ARC, are occupied by EGR transcription factors. Our previous study showed an association of the EGR family genes with schizophrenia. Collectively, the findings suggest that dysregulation in the gene expression controlled by the LDB2-EGR axis underlies a pathogenesis of subset of mental disorders.

リンク情報
DOI
https://doi.org/10.15252/emmm.202012574
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33656268
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033514
ID情報
  • DOI : 10.15252/emmm.202012574
  • PubMed ID : 33656268
  • PubMed Central 記事ID : PMC8033514

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