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Mechanism of the onset of autism by sex-specific epigenomic regulation.

Research Project

Project/Area Number 19K07365
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionKanazawa University

Principal Investigator

Horike Shin-ichi  金沢大学, 疾患モデル総合研究センター, 准教授 (40448311)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自閉症 / エピゲノム / オキシトシン / エンハンサー / エピジェネティクス / オキシトシン受容体 / エストロゲン
Outline of Research at the Start

自閉症やうつ病,不安障害などの神経発達障害における性差が生じる要因には,性染色体上の遺伝子の関与や胎児期・新生児期の脳の発達における性ホルモンの影響など複合的な要素が複雑に絡み合っていることが示唆されている。そこで,本研究課題では遺伝的要因・内分泌要因・環境要因の複合的な要因によるオキシトシン受容体遺伝子(OXTR)やバソプレッシン受容体遺伝子(AVPR)の発現制御が社会性障害や情動障害などの神経疾患発症における性差を生み出す可能性を検討する。

Outline of Final Research Achievements

It seems that the factors causing sex differences in neurodevelopmental disorders such as autism, depression, and anxiety disorders involve a complex interplay of factors such as the involvement of genes on sex chromosomes and the influence of sex hormones on brain development during the fetal and neonatal periods. In the clinical trial of oxytocin for autism, a neurodevelopmental disorder, we have revealed that the effect of oxytocin administration is stronger in males and that the effect is very broad, ranging from a very large effect among males to almost no effect among males. In this study, we performed epigenomic analysis of the OXTR and AVPR genes to investigate the possibility of generating sex differences in the development of neurological disorders such as social and emotional disorders.

Academic Significance and Societal Importance of the Research Achievements

遺伝的要因・内分泌要因・環境要因といった多面的な角度からOXTR遺伝子やAVPR遺伝子のエピゲノム解析・遺伝子発現解析を行った研究はこれまでに報告されておらず,その研究成果は自閉症やうつ病などの神経発達障害における性差の分子基盤を明らかにするだけでなく,それらの発症機序の解明にもつながることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (5 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (4 results) (of which Invited: 1 results)

  • [Int'l Joint Research] カリフォルニア大学デービス校/カリフォルニア大学サンフランシスコ校(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学デービス校(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] 天津大学(中国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] アイスランド大学(アイスランド)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] カリフォルニア大学デービス校(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes2022

    • Author(s)
      Mukai Kanae、Horike Shin-ichi、Meguro-Horike Makiko、Nakajima Yukari、Iswara Arya、Nakatani Toshio
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 3 Pages: 1-19

    • DOI

      10.1371/journal.pone.0264572

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Urinary miRNA Biomarker for Early Detection of Colorectal Cancer.2022

    • Author(s)
      Iwasaki H, Shimura T, Kitagawa M, Yamada T, Nishigaki R, Fukusada S, Okuda Y, Katano T, Horike SI, Kataoka H.
    • Journal Title

      Cancers

      Volume: 14 Issue: 2 Pages: 461-461

    • DOI

      10.3390/cancers14020461

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interferon-gamma induced APOBEC3B contributes to Merkel cell polyomavirus genome mutagenesis in Merkel cell carcinoma2021

    • Author(s)
      Que L, Li Y, Dainichi T, Kukimoto I, Nishiyama T, Nakano Y, Shima K, Suzuki T, Sato Y, Horike S, Aizaki H, Watashi K, Kato T, Aly HH, Watanabe N, Kabashima K, Wakae K, Muramatsu M.
    • Journal Title

      J Invest Dermatol

      Volume: S0022-202X(21) Issue: 7 Pages: 02636-1

    • DOI

      10.1016/j.jid.2021.12.019

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] First report of inherited protein S deficiency caused by paternal <I>PROS1</I> mosaicism2021

    • Author(s)
      Nagaya Satomi、Maruyama Keiko、Watanabe Atsushi、Meguro-Horike Makiko、Imai Yuta、Hiroshima Yuki、Horike Shin-Ichi、Kokame Koichi、Morishita Eriko
    • Journal Title

      Haematologica

      Volume: 107 Issue: 1 Pages: 330-333

    • DOI

      10.3324/haematol.2021.278527

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MUSASHI‐2 confers resistance to third‐generation EGFR‐tyrosine kinase inhibitor osimertinib in lung adenocarcinoma2021

    • Author(s)
      Yiming Reheman、Takeuchi Yasuto、Nishimura Tatsunori、Li Mengjiao、Wang Yuming、Meguro‐Horike Makiko、Kohno Takashi、Horike Shin‐ichi、Nakata Asuka、Gotoh Noriko
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 9 Pages: 3810-3821

    • DOI

      10.1111/cas.15036

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment of Retinoblastoma 1?Intact Hepatocellular Carcinoma With Cyclin‐Dependent Kinase 4/6 Inhibitor Combination Therapy2021

    • Author(s)
      Sheng Jindan、Kohno Susumu、Okada Nobuhiro、Okahashi Nobuyuki、Teranishi Kana、Matsuda Fumio、Shimizu Hiroshi、Linn Paing、Nagatani Naoko、Yamamura Minako、Harada Kenichi、Horike Shin‐ichi、Inoue Hiroshi、Yano Seiji、Kumar Sharad、Kitajima Shunsuke、Ajioka Itsuki、Takahashi Chiaki
    • Journal Title

      Hepatology

      Volume: 74 Issue: 4 Pages: 1971-1993

    • DOI

      10.1002/hep.31872

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Urinary microRNA biomarkers for detecting the presence of esophageal cancer.2021

    • Author(s)
      Okuda Y, Shimura T, Iwasaki H, Fukusada S, Nishigaki R, Kitagawa M, Katano T, Okamoto Y, Yamada T, Horike SI, Kataoka H.
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 8508-8508

    • DOI

      10.1038/s41598-021-87925-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation-induced cytidine deaminase is a possible regulator of cross-talk between oocytes and granulosa cells through GDF-9 and SCF feedback system2021

    • Author(s)
      Iizuka Takashi、Wakae Kousho、Ono Masanori、Suzuki Takuma、Mizumoto Yasunari、Kitamura Kouichi、Horike Shin-ichi、Muramatsu Masamichi、Fujiwara Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-83529-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The SNORD116 Host-Gene transcript is essential for the high order chromatin dynamics of the MAGEL2 and NDN locus over long distance2021

    • Author(s)
      堀家慎一
    • Organizer
      第44回日本小児遺伝学会学術集会,第3回日本ダウン症学会学術集会,第3回日本ダウン症会議合同学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 自閉症患者におけるオキシトシン受容体遺伝子のメチル化解析2020

    • Author(s)
      堀家 慎一
    • Organizer
      日本生化学会北陸支部第38回大会(誌上開催)
    • Related Report
      2020 Research-status Report
  • [Presentation] 自閉症患者におけるオキシトシン受容体遺伝子のメチル化解析2020

    • Author(s)
      堀家 慎一
    • Organizer
      第43回日本分子生物学会年会(オンライン)
    • Related Report
      2020 Research-status Report
  • [Presentation] 社会行動を司るオキシトシン受容体遺伝子の発現制御機構の解明2019

    • Author(s)
      有泉 桜子,目黒 牧子,山村 崇尚,岡田 源作,堀家 慎一
    • Organizer
      日本生化学会北陸支部第37回大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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