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pathophysiology of DUSP22 and MTNR1 gene abnormalities

Research Project

Project/Area Number 17K16294
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionInstitute for Developmental Research Aichi Developmental Disability Center

Principal Investigator

HAMADA NANAKO  愛知県医療療育総合センター発達障害研究所, 分子病態研究部, 研究員 (70721835)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords自閉スペクトラム症 / ASD / Dusp22 / MRTNR / DUSP22 / 自閉症 / 大脳皮質形成
Outline of Final Research Achievements

We examined the role of MTNR1A, 1B and DUSP22 in brain development and the pathophysiological significance of these gene abnormalities. Information of tissue and subcellular distribution of Dusp22 is largely unknown while information on the quality of commercially available antibodies is very limited. Therefore, we here produced a rabbit polyclonal antibody specific for Dusp22 and performed expression analyses of the molecule. While western blotting analyses clarified that Dusp22 was dominantly expressed in heart and skeletal muscle. Dusp22 was diffusely distributed in the cytoplasm and partially colocalized with actin cytoskeleton. Silencing of DUSP22 prevented dendrite development in cortical pyramidal cells in vivo. Knockdown of MTNR1A and 1B did not affected cell morphology.

Academic Significance and Societal Importance of the Research Achievements

これまで全く不明であった自閉症関連遺伝子DUSP22のマウス発達期の組織ごとの発現や細胞内局在について詳細に示すことができた。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (17 results) (of which Int'l Joint Research: 5 results) Remarks (3 results)

  • [Journal Article] Heterotrimeric G-protein, Gi1, is involved in the regulation of proliferation, neuronal migration and dendrite morphology during cortical development in vivo.2021

    • Author(s)
      Hamada N, Iwamoto I, Kawamura N, Nagata K.
    • Journal Title

      J. Neurochem.

      Volume: 1 Issue: 4 Pages: 1-1

    • DOI

      10.1111/jnc.15205

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pogz deficiency leads to transcription dysregulation and impaired cerebellar activity underlying autism-like behavior in mice.2020

    • Author(s)
      Reut Suliman-Lavie, Ben Title, Yahel Cohen, Hamada N, Maayan Tal, Nitzan Tal, Galya Monderer- Rothkoff, Bjorg Gudmundsdottir, Kristbjorn O Gudmundsson, Jonathan R Keller, Guo-Jen Huang, Nagata K, Yosef Yarom, Sagiv Shifman.
    • Journal Title

      Nat. Commun.

      Volume: 11 Issue: 1 Pages: 5836-5836

    • DOI

      10.1038/s41467-020-19577-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuropathophysiological significance of the c.1449T>C/p.(Tyr64Cys) mutation in the CDC42 gene responsible for Takenouchi-Kosaki syndrome2020

    • Author(s)
      Hamada Nanako、Ito Hidenori、Shibukawa Yukinao、Morishita Rika、Iwamoto Ikuko、Okamoto Nobuhiko、Nagata Koh-ichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 4 Pages: 1033-1037

    • DOI

      10.1016/j.bbrc.2020.06.104

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression analyses of POGZ, a responsible gene for neurodevelopmental disorders, during mouse brain development.2019

    • Author(s)
      Ibaraki K, Hamada N, Iwamoto I, Ito H, Kawamura N, Morishita R, Tabata H, Nagata KI.
    • Journal Title

      Dev Neurosci.

      Volume: 41 Issue: 1-2 Pages: 139-148

    • DOI

      10.1159/000502128

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome.2018

    • Author(s)
      Kato K, Miya F, Hamada N, Negishi Y, Kishimoto N, Ozawa H, Ito H, Hori I, Hattori A, Okamoto N, Kato M, Tsunoda T, Kanemura Y, Kosaki K, Takahashi Y, Nagata K, Saitoh S.
    • Journal Title

      J. Med. Genet

      Volume: 0 Pages: 1-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] De novo PHACTR1 mutations in West Syndrome and their pathophysiological effects.2018

    • Author(s)
      Hamada N, Ogaya S, Nakashima M, Nishijo T, Sugawara Y, Iwamoto I, Ito H, Maki Y, Shirai K, Baba S, Maruyama K, Saitsu H, Kato M, Matsumoto M, Momiyama T, Nagata K
    • Journal Title

      Brain

      Volume: 141 Pages: 3098-3114

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression analyses of Dusp22 (Dual-specificity phosphatase 22) in mouse tissues2017

    • Author(s)
      Hamada N, Mizuno M, Tomita H, Iwamoto I, Hara A, Nagata K
    • Journal Title

      Med. Mol. Morphol.

      Volume: 418 Pages: 475-481

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development2017

    • Author(s)
      Hamada N, Iwamoto I, Tabata H, Nagata K.
    • Journal Title

      Acta Neuropathologica Comm.

      Volume: 5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 発達障害関連遺伝子GNAI1の神経発達における機能解明2021

    • Author(s)
      浜田奈々子、永田浩一
    • Organizer
      日本小児遺伝学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 三量体Gタンパク質Gi1の神経発達における形態学的機能解析2020

    • Author(s)
      浜田奈々子、永田浩一
    • Organizer
      日本臨床分子形態学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Role of a heterotrimeric G-protein, Gi1, in the corticogenesis.2020

    • Author(s)
      浜田奈々子、永田浩一
    • Organizer
      日本神経化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Role of a heterotrimeric G-protein, Gαi1, regulates neurogenesis, migration and development in cortical excitatory neurons.2020

    • Author(s)
      浜田奈々子、永田浩一
    • Organizer
      日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] De novo PHACTR1 mutations in West syndrome and their pathophysiological effects2020

    • Author(s)
      浜田奈々子、大萱俊介、中島光子、西條琢磨、才津浩智、加藤光広、松本直通、籾山俊彦、永田浩一
    • Organizer
      CIBoGリトリート
    • Related Report
      2019 Research-status Report
  • [Presentation] De novo PHACTR1 mutations in West Syndrome and their pathophysiological effects.2019

    • Author(s)
      浜田奈々子、大萱俊介、中島光子、西條琢磨、才津浩智、加藤光広、松本直通、籾山俊彦、永田浩一
    • Organizer
      The 20th Annual Meeting of Infantile Seizure Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大脳皮質神経細胞の樹状突起形成におけるGαi1の役割2019

    • Author(s)
      浜田奈々子、岩本郁子、河村則子、田畑秀典、永田浩一
    • Organizer
      日本神経科学会・日本神経化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小児難治性てんかん原因遺伝子の病態生理解析2019

    • Author(s)
      浜田奈々子、大萱俊介、牧 祐輝、丸山幸一、永田浩一
    • Organizer
      日本臨床分子形態学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ウエスト症候群の新規責任遺伝子の同定と病態機能解析2019

    • Author(s)
      浜田奈々子
    • Organizer
      小児遺伝学会
    • Related Report
      2018 Research-status Report
  • [Presentation] De novo PHACTR1 mutations in West Syndrome and their pathophysiological effects.2018

    • Author(s)
      永田浩一
    • Organizer
      Society for neuroscience 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of PHACTR1 as a novel causal gene for West Syndrome and pathophysiological significance of the gene mutations2018

    • Author(s)
      浜田奈々子
    • Organizer
      日本神経化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児難治性てんかん責任遺伝子の病態生理解析2018

    • Author(s)
      浜田奈々子
    • Organizer
      生理学研究所研究会「神経発達・再生研究会」
    • Related Report
      2018 Research-status Report
  • [Presentation] Munc18-1 plays an essential role for cortical neuron migration during brain development2017

    • Author(s)
      浜田奈々子、田畑秀典、永田浩一
    • Organizer
      日本神経化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of Munc18-1 in cortical neuron migration2017

    • Author(s)
      浜田奈々子、田畑秀典、永田浩一
    • Organizer
      日本生化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of MUNC18-1 in brain development and involvement in early infantile epilepsies2017

    • Author(s)
      Koh-Ichi Nagata and Nanako Hamada
    • Organizer
      Excitatory Synapses & Brain Function
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathophysiological significance of early infantile epilepsies caused by MUNC18-1 mutations2017

    • Author(s)
      Koh-Ichi Nagata and Nanako Hamada
    • Organizer
      48th ASN Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathophysiological mechanism of MUNC18-1 mutations in early infantile epilepsies2017

    • Author(s)
      Koh-Ichi Nagata and Nanako Hamada
    • Organizer
      ISN-ESN Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 発達障害研究所分子病態研究部

    • URL

      https://www.pref.aichi.jp/addc/eachfacility/hattatsu/department/index4.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 愛知県医療療育総合センター発達障害研究所

    • URL

      https://www.pref.aichi.jp/addc/eachfacility/hattatsu/index.html

    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Remarks] 発達障害研究所神経制御学部の紹介

    • URL

      http://www.inst-hsc.jp/d-molecular/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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