Elucidation of integrated molecular mechanisms of sleep/wakefullness and metabolic control in newly established Sleepy mouse

• Project/Area Number: 26507003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 睡眠科学
• Research Institution: University 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, 教授(WPI-IIIS) (90363118)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 睡眠 / フォワード・ジェネティクス / 肥満 / フォワードジェネティクス

Outline of Final Research Achievements

We established Sleepy mutant pedigree showing shorter wake time compared to the mean of all mice screened through the large-scale forward-genetic screening. Sleepy mice have a mutation in the AMP-activated kinase-related kinase Sik3 gene. This year, we reported a new function of Sleepy mutant Sik3 gene in sleep behavior. This pedigree of mouse shows obesity as well as shorter wake time. The QTL analysis identified a mutation related to the abnormal sleep phenotype in the same chromosome region responsible for body weight phenotype. Sleepy mutant mice showed a significant decrease in energy consumption, though no difference was found in food intake. There are various reports on the relationship between sleep and obesity. Since the onset age of the phenotype is different, it may be essential to examine spatiotemporal changes comparing various experimental conditions, such as the site of expression of Sleepy-mutant SIK3 in the brain, timing of sampling, quantitative change of expression.

Research Products

• [Journal Article] Forward-genetics analysis of sleep in randomly mutagenized mice (2016)
  • Author(s): Funato H and Yanagisawa M et al.
  • Journal Title: Nature Volume: 539(7629) Issue: 46 Pages: 378-383
  • DOI: 10.1038/nature20142
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phase I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine (2016)
  • Author(s): Ikeda M, Sato A, Mochizuki N, Toyosaki K, Miyoshi C, Fujioka R, Mitsunaga S, Ohno I, Hashimoto Y, Takahashi H, Hasegawa H, Nomura S, Takahashi R, Yomoda S, Tsuchihara K, Kishino S, Esumi H
  • Journal Title: Cancer Science Volume: 107(12) Issue: 12 Pages: 1818-1824
  • DOI: 10.1111/cas.13086
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of mutations through dominant screening for obesity using C57BL/6 substrains (2016)
  • Author(s): Hossain MS., Funato H, and Yanagisawa M et al.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 32453-32453
  • DOI: 10.1038/srep32453
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] フォワード・ジェネティクスによる過眠と肥満をもたらす遺伝子変異の同定 (2017)
  • Author(s): 船戸弘正
  • Organizer: 第23回日本行動医学会学術総会・シンポジウム「健康に及ぼす睡眠と食との相互作用」
  • Place of Presentation: 沖縄科学技術大学院大学(恩納村）
  • Invited
• [Presentation] 睡眠異常を示す新規2型糖尿病モデルマウスの解析と予防的介入法の検討 (2016)
  • Author(s): 管野里美、三好千香、佐藤牧人、原野加奈子、一久綾、堀田範子、柿崎美代、高橋智、若菜茂晴、船戸弘正、柳沢正史
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-11-30
• [Presentation] 離乳前若年齢マウスの脳波・筋電測定法の開発 (2016)
  • Author(s): 堀田範子、三好千香、佐藤牧人、一久綾、管野里美、船戸弘正、柳沢正史
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-11-30
• [Presentation] 新規睡眠制御分子Sleepyのリン酸化状態の解析 (2016)
  • Author(s): 一久綾、堀田範子、佐藤牧人、三好千香、管野里美、柿崎美代、船戸弘正、柳沢正史
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-11-30
• [Presentation] Forward genetics approach in identification of novel sleep/wakefulness related gene(s) (2016)
  • Author(s): Hiromasa Funato, Chika Miyoshi, Makito Sato, Noriko Hotta, Satomi Kanno, Aya Ikkyu Miyo Kakizaki, Komiya Haruna, Shigeharu Wakana, Masashi Yanagisawa
  • Organizer: Neuroscience 2016,
  • Place of Presentation: Convention center, San Diego, USA
  • Year and Date: 2016-11-16
  • Int'l Joint Research
• [Presentation] Forward genetics approach in identification of novel sleep/wakefulness related gene(s) (2016)
  • Author(s): Staci J. Kim, Tomoyuki Fujiyama, Chika Miyoshi, Noriko Hotta, Satomi Kanno, Aya Ikkyu, Miyo Kakizaki, Taeko Matsuoka, Seiya Mizuno, Ikuo Miura, Tomoyuki Suzuki, Vivek Kumar, Joseph S. Takahashi, Satoru Takahashi, Shigeharu Wakana, Hiromasa Funato, Masashi Yanagisawa
  • Organizer: Neuroscience 2016
  • Place of Presentation: Convention center, San Diego, USA
  • Year and Date: 2016-11-14
  • Int'l Joint Research
• [Presentation] Identification of Mc4r mutation through obesity screening of ENU-mutagenized mice (2016)
  • Author(s): Mohammad Sarowar Hossain, Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Makito Sato, Aya Ikkyu, Satomi Kanno, Noriko Hotta, Miyo Kakizaki, Ikuo Miura, Hideki Kaneda, Tomohiro Suzuki, Shigeharu Wakana, Hiromasa Funato, Masashi Yanagisawa
  • Organizer: 第121回日本解剖学会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
• [Presentation] ランダム点突然変異マウスの肥満スクリーニングによるSim1遺伝子変異の同定 (2016)
  • Author(s): 浅野冬樹,Mohammad Sarowar Hossain, 藤山知之, 三好千香, 佐藤牧人, 一久綾, 管野里美, 堀田範子, 柿崎美代, 三浦郁生, 金田秀貴, 鈴木智広, 若菜茂晴, 船戸弘正, 柳沢正史
  • Organizer: 第121回日本解剖学会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
• [Presentation] Sleep screening of randomly mutagenized mice established a long sleep pedigree. (2016)
  • Author(s): Chika Miyoshi, Tomoyuki Fujiyama, Makito Sato, Aya Ikkyu, Satomi Kanno, Noriko Hotta, Miyo Kakizaki, Takato Honda, Staci J. Kim, Haruna Komiya, Fuyuki Asano, Tomohiro Suzuki, Kumar Vivek, Joseph S. Takahashi, Shigeharu Wakana, Hiromasa Funato, Masashi Yanagisawa
  • Organizer: The 4th Annual IIIS International Symposium.
  • Place of Presentation: 筑波大学（茨城県つくば市）
  • Year and Date: 2016-02-26
  • Int'l Joint Research
• [Presentation] Identification of Sim1 and Mc4r mutations through obesity screening of randomly mutagenized mice (2016)
  • Author(s): Mohammad Sarowar Hussain, Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Makito Sato, Aya Ikkyu, Satomi Kanno, Noriko Hotta, Miyo Kakizaki, Takato Honda, Staci J. Kim, Haruna Komiya, Ikuo Miura, Tomohiro Suzuki, Kumar Vivek, Joseph S. Takahashi, Shigeharu Wakana, Hiromasa Funato, Masashi Yanagisawa
  • Organizer: The 4th Annual IIIS International Symposium.
  • Place of Presentation: 筑波大学（茨城県つくば市）
  • Year and Date: 2016-02-26
  • Int'l Joint Research
• [Presentation] Identification of a single nucleotide substitution specific to the Dreamless mutant mouse by linkage analysis and whole exome sequencing and its genetic verification by CRISPR (2016)
  • Author(s): Tomoyuki Fujiyama, et, al.
  • Organizer: The 4th Annual IIIS International Symposium.
  • Place of Presentation: 筑波大学（茨城県つくば市）
  • Year and Date: 2016-02-26
  • Int'l Joint Research
• [Presentation] Understanding the molecular basis of fear and the role of emotion in sleep regulation (2016)
  • Author(s): Liqin Cao, Daniela Klewe-Nebenius, Andong Tang, Chika Miyoshi, Hiromasa Funato, Masashi Yanagisawa, Qinghua Liu
  • Organizer: The 4th Annual IIIS International Symposium.
  • Place of Presentation: 筑波大学（茨城県つくば市）
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Systematic behavioral screening of Sleepy and Dreamless, newly identified mouse pedigrees with sleep abnormalities (2016)
  • Author(s): Takato Honda, Tomoyuki Fujiyama, Chika Miyoshi, Makito Sato, Hiromasa Funato, Masashi Yanagisawa
  • Organizer: The 4th Annual IIIS International Symposium.
  • Place of Presentation: 筑波大学（茨城県つくば市）
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Identification and recapitulation of a single nucleotide substitution specific to the Dreamless mutant mouse pedigree by linkage analysis, whole exome sequencing and CRISPR. (2015)
  • Author(s): 藤山知之 船戸弘正 三好千香 佐藤牧人 水野聖哉 上田壮志 高橋智 村本玄紀 Qinghua Liu 一久綾 堀田範子 柿崎美代 管野里美 石川有紀子 浅野冬樹 本多隆利 鈴木智広 若菜茂晴 柳沢正史
  • Organizer: 第3８回日本神経科学学会学術総会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-28