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Integrated Molecular Mechanisms of Sleep/Wakefulness and Metabolic Regulation in a Novel Hypersomnia and Obese Mouse Model

Research Project

Project/Area Number 18K06024
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Miyoshi Chika  筑波大学, 国際統合睡眠医科学研究機構, 助教 (60613437)

Co-Investigator(Kenkyū-buntansha) 船戸 弘正  筑波大学, 国際統合睡眠医科学研究機構, 客員教授 (90363118)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords過眠 / 肥満 / 睡眠
Outline of Final Research Achievements

In sleepy mutant SIK3 mice, obesity is observed from young age with hypersomnia. In this study, to elucidate the mechanisms underlying the appearance and regulation of hypersomnia and obesity, we investigated the molecular network involved in their regulation by cell type-specific sleepy expression in a spatiotemporal manner.
In brain neuron-specific and peripheral tissue-specific cre mice, the hypersomnia phenotype of systemic type of sleepy mice was reproduced only by the expression of a type of cranial neuron-specific sleepy, while peripheral expression did not alter sleep duration or EEG spectrum components. The obesity phenotype was also not a peripheral function, suggesting that the hypersomnolence and obesity phenotypes in Sleepy mice are neuronal control of the brain.

Academic Significance and Societal Importance of the Research Achievements

睡眠は心身の健康を保ち、質の高い社会生活を送ることに不可欠である。不眠等の睡眠障害は、わが国でも広く認められており、うつ病などの気分障害、メタボリック症候群との関連も深い。睡眠覚醒行動の異常と摂食行動の障害とは密接に関係すると考えられるが、その分子機構は明らかではない。よいモデル動物が得られれば、睡眠覚醒行動や摂食行動など、異なる行動モダリティーを制御する統合的な研究が可能になると考えられた。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (14 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Metabolomic and pharmacologic analyses of brain substances associated with sleep pressure in mice2022

    • Author(s)
      Suzuki-Abe Haruka、Sonomura Kazuhiro、Nakata Shinya、Miyanishi Kazuya、Mahmoud Asmaa、Hotta-Hirashima Noriko、Miyoshi Chika、Sato Taka-Aki、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Neuroscience Research

      Volume: 177 Pages: 16-24

    • DOI

      10.1016/j.neures.2021.11.008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of Mutant Sik3Sleepy Allele in Neurons in Late Infancy Increases Sleep Need2021

    • Author(s)
      Iwasaki Kanako, Fujiyama Tomoyuki, Nakata Shinya, Park Minjeong, Miyoshi Chika, Hotta-Hirashima Noriko, Ikkyu Aya, Kakizaki Miyo, Sugiyama Fumihiro, Mizuno Seiya, Abe Manabu, Sakimura Kenji, Takahashi Satoru, Funato Hiromasa, Yanagisawa Masashi
    • Journal Title

      The Journal of Neuroscience

      Volume: 41 Issue: 12 Pages: 2733-2746

    • DOI

      10.1523/jneurosci.1004-20.2020

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Reproductive Hormones in Sex Differences in Sleep Homeostasis and Arousal Response in Mice2021

    • Author(s)
      Choi Jinhwan、Kim Staci J.、Fujiyama Tomoyuki、Miyoshi Chika、Park Minjeong、Suzuki-Abe Haruka、Yanagisawa Masashi、Funato Hiromasa
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 739236-739236

    • DOI

      10.3389/fnins.2021.739236

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two novel mouse models mimicking minor deletions in 22q11.2 deletion syndrome revealed the contribution of each deleted region to psychiatric disorders2021

    • Author(s)
      Saito Ryo、Miyoshi Chika、Koebis Michinori、Kushima Itaru、Nakao Kazuki、Mori Daisuke、Ozaki Norio、Funato Hiromasa、Yanagisawa Masashi、Aiba Atsu
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 68-68

    • DOI

      10.1186/s13041-021-00778-7

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In Vivo.2020

    • Author(s)
      Omori S, Wang TW, Johmura Y, ..., Sakamoto T (15番目), ..., Nakanishi M.
    • Journal Title

      Cell Metab

      Volume: 32 Issue: 5 Pages: 814-828

    • DOI

      10.1016/j.cmet.2020.09.006

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need2020

    • Author(s)
      Park Minjeong, Miyoshi Chika, Fujiyama Tomoyuki, Kakizaki Miyo, Ikkyu Aya, Honda Takato, Choi Jinhwan, Asano Fuyuki, Mizuno Seiya, Takahashi Satoru, Yanagisawa Masashi, Funato Hiromasa
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8676-8676

    • DOI

      10.1038/s41598-020-65647-0

    • NAID

      120007163335

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice2020

    • Author(s)
      Yukino Ogawa, Chika Miyoshi, Nozomu Obana, Kaho Yajima, Noriko Hotta-Hirashima, Aya Ikkyu, Satomi Kanno, Tomoyoshi Soga, Shinji Fukuda & Masashi Yanagisawa
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 19554-19554

    • DOI

      10.1038/s41598-020-76562-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice.2019

    • Author(s)
      Miyoshi C, Kim SJ, Ezaki T, Ikkyu A, Hotta-Hirashima N, Kanno S, Kakizaki M, Yamada M, Wakana S, Yanagisawa M, Funato H
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 32 Pages: 16062-16067

    • DOI

      10.1073/pnas.1906774116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A single phosphorylation site of SIK3 regulates daily sleep amounts and sleep need in mice2018

    • Author(s)
      Honda Takato、Fujiyama Tomoyuki、Miyoshi Chika、Ikkyu Aya、Hotta-Hirashima Noriko、Kanno Satomi、Mizuno Seiya、Sugiyama Fumihiro、Takahashi Satoru、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 41 Pages: 10458-10463

    • DOI

      10.1073/pnas.1810823115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response2018

    • Author(s)
      Iwasaki Kanako、Komiya Haruna、Kakizaki Miyo、Miyoshi Chika、Abe Manabu、Sakimura Kenji、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 12 Pages: 535-535

    • DOI

      10.3389/fnins.2018.00535

    • NAID

      120007133025

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative phosphoproteomic analysis of the molecular substrates of sleep need2018

    • Author(s)
      Z. Wang, J. Ma, C. Miyoshi, Y. Li, M Sato, Y. Ogawa, T. Lou, C. Ma, X. Gao, C. Lee, T. Fujiyama, X. Yang, S. Zhou, N. Hotta-Hirashima, D. Klewe-Nebenus, A. Ikkyu, M. Kakizaki, S. Kanno, L. Cao, S. Takahashi, J. Peng, Y. Yu, H. Funato, M. Yanagisawa, Q. Liu
    • Journal Title

      Nature

      Volume: 558 Issue: 7710 Pages: 435-439

    • DOI

      10.1038/s41586-018-0218-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors2018

    • Author(s)
      Wang, Y., Cao, L., Lee, C-Y., Matsuo, M., Wu, K., Asher, G., Saitoh, T., Klewe-Nebenius, D., Wang, L., Soya, S., Hasegawa, E., Cherasse, Y., Miyoshi,C., Irukayama, Y., Wang, Z., Sakurai, K., Funato, H., Sakurai, T., Yanagisawa, M., Nagase, H., Kobayakawa, R., Kobayakawa, K., Beutler, B., Liu, Q
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2041-2041

    • DOI

      10.1038/s41467-018-04324-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] フォワードジェネティクスの手法を用いた睡眠スクリーニングによる過眠・肥満マウスモデル 家系の確立2022

    • Author(s)
      Chika Miyoshi, Noriko Hotta-Hirashim, Aya Ikkyu, Miyo Kakizaki, Satomi Kanno, Masashi Yanagisawa and Hiromasa Funato
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of a Model Mouse Pedigree with Hypersomnia, Sleepy, by Large-Scale Forward Genetic Screening2019

    • Author(s)
      Miyoshi C, Hotta-Hirashima N, Ikkyu A,Kanno S, Kakizaki M,Yamada M, Kim SJ, Ezaki T,Wakana S, Funato H,Yanagisawa M
    • Organizer
      8th Japan-Sino-Korea Mouse Resource Workshop
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of Screening Method for Sleep/Wakefullness in Mice Through Forward Genetics.2019

    • Author(s)
      Miyoshi C, Hotta-Hirashima N, Kanno S, Ikkyu A,Kakizaki M,Yamada M,Kim SJ, Wakana S, Yanagisawa M, Funato H
    • Organizer
      97th Annual Meeting of the Physiological Society of Japan
    • Related Report
      2019 Research-status Report
  • [Presentation] Effect of central serotonergic ablation on sleep/wake behavior in mice2018

    • Author(s)
      Kanako Iwasaki, Haruna Komiya, Miyo Kakizaki, Chika Miyoshi, Manabu Abe, Kenji Sakimura, Hiromasa Funato, and Masashi Yanagisawa
    • Organizer
      The 41st Annual Meeting of Japan Neuroscience Society
    • Related Report
      2018 Research-status Report
  • [Presentation] Identification of a novel gene family in sleep and wake regulation2018

    • Author(s)
      Staci J. Kim, Tomoyuki Fujiyama, Chika Miyoshi, Noriko Hotta-Hirashima, Satomi Kanno, Aya Ikkyu, Miyo Kakizaki, Seiya Mizuno, Satoru Takahashi, Hiromasa Funato, and Masashi Yanagisawa
    • Organizer
      The 41st Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2018 Research-status Report
  • [Presentation] Forward genes study identifies novel gene in sleep/wake regulation2018

    • Author(s)
      Staci J. Kim, Tomoyuki Fujiyama, Chika Miyoshi, Noriko Hotta-Hirashima, Satomi Kanno, Aya Ikkyu, Miyo Kakizaki, Seiya Mizuno, Satoru Takahashi, Hiromasa Funato, and Masashi Yanagisawa
    • Organizer
      2018 Korean Society for Molecular and Cellular Biology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of the neuron-type specific SIK3-deficient mice2018

    • Author(s)
      Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Miyo Kakizaki, Noriko Hotta-Hirashima, Aya Ikkyu, Satomi Kanno, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
    • Organizer
      Tsukuba Global Science Week(TGSW) 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Sik1, Sik2, point mutation mice -Paralog analysis of Sik3 gene in Sleepy Mutant pedigree2018

    • Author(s)
      Minjeong Park, Chika Miyoshi, Tomoyuki Fujiyama, Miyo Kakizaki, Aya Ikkyu, Takato Honda, Jinhwan Choi,Seiya Mizuno, Kanako Kato, Yoko Taimoto, Hiromasa Funato, and Masashi Yanagisawa
    • Organizer
      Tsukuba Global Science Week(TGSW) 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Production of brain-specific SIK3-deficient mice2018

    • Author(s)
      Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Miyo Kakizaki, Noriko Hotta-Hirashima, Aya Ikkyu, Satomi Kanno, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
    • Organizer
      The 41st Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2018 Research-status Report
  • [Presentation] Sleep arousal behavior of SIK1 and SIK2 PKA phosphorylation site mutated mice2018

    • Author(s)
      Staci J. Kim, Tomoyuki Fujiyama, Chika Miyoshi, Noriko Hotta-Hirashima, Satomi Kanno, Aya Ikkyu, Miyo Kakizaki, Hiromasa Funato, and Masashi Yanagisawa&
    • Organizer
      The 41st Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2018 Research-status Report
  • [Presentation] Title: Where does the Dreamless mutation take effect?2018

    • Author(s)
      Tomoyuki Fujiyama, Seiya Mizuno, Manabu Abe, Satomi Kanno, Miyo Kakizaki, Kanako Iwasaki, Aya Ikkyu, Noriko Hotta-Hirashima, Mana Yamada, Chika Miyoshi, Makito Sato, Takeshi Kanda, Kenji Sakimura, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
    • Organizer
      The 7th IIIS Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Investigation of Sleep/Wake Regulatory Mechanisms by Analysis of the Sik3 Gene Identified Through Forward Genetics2018

    • Author(s)
      Takato Honda, Tomoyuki Fujiyama, Chika Miyoshi, Aya Ikkyu, Noriko Hotta, Satomi Kanno, Hiromasa Funato and Masashi Yanagisawa
    • Organizer
      The 41st Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2018 Research-status Report
  • [Presentation] Investigation of Sleep/Wake Regulatory Mechanisms by Analysis of the Sik3 Gene Identified Through Forward Genetics2018

    • Author(s)
      Takato Honda, Tomoyuki Fujiyama, Chika Miyoshi, Aya Ikkyu, Noriko Hotta, Satomi Kanno, Hiromasa Funato and Masashi Yanagisawa
    • Organizer
      The 43rd Japanese Society of Sleep Research jointly held with The 9th Asian Sleep Research Society Asian Forum on Chronobiology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ablation of central serotonergic neurons decreased REM sleep and attenuated arousal response2018

    • Author(s)
      Kanako Iwasaki, Haruna Komiya, Miyo Kakizaki, Chika Miyoshi, Manabu Abe, Kenji Sakimura, Hiromasa Funato, and Masashi Yanagisawa
    • Organizer
      Tsukuba Global Science Week(TGSW) 2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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