Development of basic technologies for new in vivo imaging to promote life science research

• Project/Area Number: 21220009
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: University of Tsukuba
• Principal Investigator: TAKAHASHI Satoru 筑波大学, 医学医療系, 教授 (50271896)
• Co-Investigator(Kenkyū-buntansha): YAGAMI Ken-ichi 筑波大学, 医学医療系, 教授 (40166476) ; ICHIJO Hiroyuki 富山大学, 大学院医学薬学研究部(医学), 教授 (40272190) ; MIWA Yoshihiro 筑波大学, 医学医療系, 講師 (70263845) ; SUGIYAMA Fumihiro 筑波大学, 医学医療系, 准教授 (90226481)
• Co-Investigator(Renkei-kenkyūsha): EMA Masatsugu 滋賀医科大学, 動物生命科学研究センター, 教授 (60359578)
• Project Period (FY): 2009-05-11 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥187,460,000 (Direct Cost: ¥144,200,000、Indirect Cost: ¥43,260,000); Fiscal Year 2013: ¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000); Fiscal Year 2012: ¥34,320,000 (Direct Cost: ¥26,400,000、Indirect Cost: ¥7,920,000); Fiscal Year 2011: ¥34,320,000 (Direct Cost: ¥26,400,000、Indirect Cost: ¥7,920,000); Fiscal Year 2010: ¥34,320,000 (Direct Cost: ¥26,400,000、Indirect Cost: ¥7,920,000); Fiscal Year 2009: ¥57,460,000 (Direct Cost: ¥44,200,000、Indirect Cost: ¥13,260,000)
• Keywords: 応用動物 / バイオテクノロジー / 動物 / 遺伝子 / 神経科学 / 蛍光イメージング / Tgマウス / 動物モデル / 神経活動 / 薬物動態 / in vivoイメージング / 蛍光タンパク質 / 発光タンパク質 / 遺伝子改変マウス

Research Abstract

In this application, using a variety of florescence-labeled proteins and genetic engineering strategies that have not been practically used, we attempted to develop new in vivo imaging methods. Electrophysiological and histological analyses most often have been used for studies in neuroscience. However, using a new fluorescence labeling technology, we developed a system to monitor history of neuronal activity, which has not been feasible to date by using gene-manipulated mice.

Assessment Rating

Verification Result (Rating)

A

Research Products

• [Journal Article] Generation and Characterization of Ins1-cre-driver C57BL/6N for Exclusive Pancreatic Beta Cell-specific Cre-loxP Recombination (2014)
  • Author(s): Hasegawa Y, Daitoku Y, Mizuno S, Tanimoto Y, Mizuno-Iijima S, Matsuo M, Kajiwara N, Ema M, Oishi H, Miwa Y, Mekada K, Yoshiki A, Takahashi S, Sugiyama F, Yagami K
  • Journal Title: Exp Animal Volume: 63 Pages: 183-191
  • NAID: 130003391621
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24770644
  • Peer Reviewed
• [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis (2014)
  • Author(s): Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano H, Miyazaki T, Tontonz P, Takahashi S
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 3147-3147
  • DOI: 10.1038/ncomms4147
  • Peer Reviewed / Open Access
• [Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis. (2014)
  • Author(s): Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano H, Miyazaki T, Tontonz P, Takahashi S.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3147-3147
  • DOI: 10.1038/ncomms4149
  • Peer Reviewed
• [Journal Article] Novel ROSA26 Cre-reporter knock-in C57BL/6N mice exhibiting green emission before and red emission after Cre-mediated recombination (2013)
  • Author(s): Hasegawa Y, Daitoku Y, Sekiguchi K, Tanimoto Y, Iijima S, Mizuno S, Kajiwara N, Ema M, Miwa Y, Mekada K, Yoshiki A, Takahashi S, Sugiyama F, Yagami K-I
  • Journal Title: Exp Animal Volume: 62 Pages: 295-304
  • NAID: 130003382716
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Hasegawa+Y%2C+Daitoku+Y%2C+Sekiguchi+K
  • Peer Reviewed
• [Journal Article] Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method (2013)
  • Author(s): Hamanaka S, Ooehara J, Morita Y, Ema H, Takahashi S, Miyawaki A, Otsu M, Yamaguchi T, Onodera M, Nakauchi H
  • Journal Title: Biochem Biophys Res Commun Volume: i435(4) Issue: 4 Pages: 586-91
  • DOI: 10.1016/j.bbrc.2013.05.017
  • Peer Reviewed
• [Journal Article] In vivo monitoring of pancreatic β -cell mass and intrahepatic insulin gene activity in Ins1-luc BAC transgenic mice by bioluminescence imaging (2013)
  • Author(s): Katsumata T, Oishi H, Sekiguchi Y, Nagasaki H, Daassi D, Ema M, Kudo T, Takahashi S
  • Journal Title: Plos One Volume: 8 Issue: 4 Pages: e60411-e60411
  • DOI: 10.1371/journal.pone.0060411
  • Peer Reviewed
• [Journal Article] In vivo monitoring of pancreatic β-cell mass and intrahepatic insulin gene activity in Ins1-luc BAC transgenic mice by bioluminescence imaging. (2013)
  • Author(s): Katsumata T, Oishi H, Sekiguchi Y, Nagasaki H, Daassi D, Ema M, Kudo T, Takahashi S.
  • Journal Title: Plos One Volume: 8
  • Peer Reviewed
• [Journal Article] Novel ROSA26 Cre-reporter knock-in C57BL/6N mice exhibiting green emission before and red emission after Cre-mediated recombination. (2013)
  • Author(s): Hasegawa Y, Daitoku Y, Sekiguchi K, Tanimoto Y, Iijima S, Mizuno S, Kajiwara N, Ema M, Miwa Y, Mekada K, Yoshiki A, Takahashi S, Sugiyama F, Yagami K-i.
  • Journal Title: Experimental Animals Volume: 62 Pages: 295-304
  • NAID: 130003382716
  • Peer Reviewed
• [Journal Article] In vivo monitoring of pancreatic β-cell mass and intrahepatic insulin gene activity in Ins1-luc BAC transgenic mice by bioluminescence imaging. (2013)
  • Author(s): Katsumata T
  • Journal Title: Plos One Volume: 8(4)
  • Peer Reviewed
• [Journal Article] Genome-wide identification of endothelial cell-enriched genes in the mouse embryo (2012)
  • Author(s): Takase H, Matsumoto H, Yamadera R, Kubota Y, Otsu A, Suzuki R, Ishitobi H, Mochizuki H, Kojima T, Takano S, Uchida K, Takahashi S, Ema M
  • Journal Title: Blood Volume: 120 Issue: 4 Pages: 914-923
  • DOI: 10.1182/blood-2011-12-398156
  • Peer Reviewed
• [Journal Article] Study of normal and pathological blood vessel morphogenesis in Flt1-tdsRed BAC Tg mice (2012)
  • Author(s): Matsumoto K, Azami T, Otsu A, Takase H, Ishitobi H, Tanaka J, Miwa Y, Takahashi S, Ema M
  • Journal Title: Genesis Volume: 50 Issue: 7 Pages: 561-571
  • DOI: 10.1002/dvg.22031
  • Peer Reviewed
• [Journal Article] Non-invasive monitoring of β-cell mass and fetal β -cell genesis in mouse using bioluminescence imaging (2012)
  • Author(s): Sekiguchi Y, Owada J, Oishi H, Katsumata T, Ikeda R, Kudo T, Takahashi S
  • Journal Title: Exp Animal Volume: 61 Pages: 445-451
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Sekiguchi+Y%2C+Owada+J%2C+Oishi+H
  • Peer Reviewed
• [Journal Article] Study of normal and pathological blood vessel morphogenesis in Flt1-tdsRed BAC Tg mice. (2012)
  • Author(s): Matsumoto K
  • Journal Title: Genesis Volume: 50(7) Pages: 561-571
  • Peer Reviewed
• [Journal Article] Study of normal and pathological blood vessel morphogenesis in Flt1-tdsRed BAC Tg mice (2012)
  • Author(s): Matsumoto K, et al.
  • Journal Title: Genesis Volume: (in press)
  • Peer Reviewed
• [Journal Article] Genome-wide identification of vascular endothelial-specific genes during development in the mouse (2012)
  • Author(s): Takase H, et al
  • Journal Title: Blood Volume: (in press)
  • Peer Reviewed
• [Journal Article] Non-invasive monitoring of β-cell mass and fetal b-cell genesis in mouse using bioluminescence imaging (2012)
  • Author(s): Sekiguchi Y, et al.
  • Journal Title: Exp Animal Volume: (in press)
  • Peer Reviewed
• [Journal Article] Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse (2011)
  • Author(s): Ishitobi H, Wakamatsu A, Lui F, Azami T, Hamada M, Matsumoto K, Kataoka H, kobayashi M, Choi K, Nishikawa S-I, Takahashi S, Ema M
  • Journal Title: Development Volume: 138 Issue: 24 Pages: 5357-5368
  • DOI: 10.1242/dev.065565
  • Peer Reviewed
• [Journal Article] MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development (2011)
  • Author(s): Kamitani-Kawamoto A, Hamada M, Moriguchi T, Miyai M, Hitoshi S, Ikenaka K, Hosoya T, Hotta Y, Takahashi S, Kataoka K
  • Journal Title: J Bone Mineral Res Volume: 26 Issue: 10 Pages: 2463-2472
  • DOI: 10.1002/jbmr.458
  • Peer Reviewed
• [Journal Article] Indefinite self-renewal of ES cells through Myc/Max transcriptional complexes-independent mechanisms (2011)
  • Author(s): Hishida T, Nozaki Y, Nakachi Y, Mizuno Y, Okazaki Y, Ema M, Takahashi S, Nishimoto M, Okuda A
  • Journal Title: Cell Stem Cell Volume: 9 Issue: 8 Pages: 37-49
  • DOI: 10.1002/stem.1147
  • Peer Reviewed
• [Journal Article] Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero (2011)
  • Author(s): Kubota Y, Takubo K, Hirashima M, Nagoshi N, Kishi K, Sano K, Murakami M, Ema M, Omatsu Y, Takahashi S, Nagasawa T, Shibuya M, Okano H, Suda T
  • Journal Title: J Exp Med Volume: 208 Issue: 5 Pages: 949-960
  • DOI: 10.1084/jem.20102187
  • Peer Reviewed
• [Journal Article] Two distinct origins for Leydig cell progenitors in the fetal testis (2011)
  • Author(s): DeFalco T, Takahashi S, Capel B
  • Journal Title: Dev Biol Volume: 352 Issue: 1 Pages: 14-26
  • DOI: 10.1016/j.ydbio.2011.01.011
  • Peer Reviewed
• [Journal Article] Recruitment of vascular precursors marked by myelin protein zero in postnatal vasculogenesis. (2011)
  • Author(s): Kubota Y, et al.
  • Journal Title: J Exp Med. Volume: in press
  • Peer Reviewed
• [Journal Article] Flk1-GFP BAC Tg mice : an animal model for the study of blood vessel development (2010)
  • Author(s): Ishitobi H, Matsumoto K, Azami T, Itoh F, Itoh S, Takahashi S, Ema M
  • Journal Title: Exp Anim (Experimental Animals(日本実験動物学会機関誌)2010年最優秀論文賞受賞 ) Volume: 59 Pages: 615-622
  • NAID: 130000419256
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21030789
  • Peer Reviewed
• [Journal Article] Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum. (2010)
  • Author(s): Kojima T, et al.
  • Journal Title: Stem Cell. Volume: 28 Pages: 545-554
  • Peer Reviewed
• [Journal Article] Flkl-GFP BAC Tg mice: an animal model for the study of blood vesseldevelopment. (2010)
  • Author(s): Ishitobi H, et al.
  • Journal Title: Exp Anim. Volume: 59 Pages: 615-622
  • Peer Reviewed
• [Journal Article] Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum. (2010)
  • Author(s): Kojima T, et al.
  • Journal Title: Stem Cell. 28 Pages: 545-554
  • Peer Reviewed
• [Journal Article] Tsukuba-green : A Fluorescent Dye that Emits Green Fluorescence Useful for Live-cell Imaging (2010)
  • Author(s): Senda N, et al.
  • Journal Title: Chem.Lett. 39 Pages: 308-310
  • Peer Reviewed
• [Journal Article] 蛍光タンパク質を用いた分子スイッチ機能を応用するイメージング法の開発 (2009)
  • Author(s): 戸村道夫
  • Journal Title: 分析化学 58 Pages: 447-460
  • Peer Reviewed
• [Presentation] 血管内皮細胞を可視化するためのFlk1-GFPおよびFlt1-tdsRed BACトランスジェニックマウスの作製 (2013)
  • Author(s): 松本健、浅見拓哉、高橋智、依馬正次
  • Organizer: 実験動物学会
  • Place of Presentation: つくば
• [Presentation] 生物発光イメージングを用いた膵β細胞および肝内インスリン遺伝子発現の可視化 (2013)
  • Author(s): 大石久史、勝又斗紀夫、関口有佳里、長崎はるか、ダーシドーハ、依馬正次、工藤 崇、高橋 智
  • Organizer: 実験動物学会
  • Place of Presentation: つくば
• [Presentation] Cre/loxP遺伝子組換え前後を異なる蛍光タンパク質でモニターするRosa26ノックインマウスC57BL/6Nマウス (2013)
  • Author(s): 大徳陽子、長谷川賀一、谷本陽子、村上亞弓、門田雅世、橋本知美、目加田和之、中田初美、吉木淳、三輪佳宏、依馬正次、水野聖哉、杉山文博、八神健一、高橋 智
  • Organizer: 実験動物学会
  • Place of Presentation: つくば
• [Presentation] MafBは動脈硬化発症において泡沫細胞の生存に重要である (2012)
  • Author(s): 中村恵弥、濱田理人、勝又斗紀夫、澤口恭子、白石莉紗子、工藤崇、高橋智
  • Organizer: 実験動物学会
  • Place of Presentation: 別府
• [Presentation] 生物発光イメージングによるIns1-luc-BACトランスジェニックマウスを用いた膵β細胞量と肝臓でのインスリン遺伝子発現活性化能の検出 (2012)
  • Author(s): 勝又斗紀夫、大石久史、関口有佳里、長崎はるか、ダーシドーハ、依馬正次、工藤 崇、高橋 智
  • Organizer: 分子生物学会
  • Place of Presentation: 福岡
• [Presentation] 血管内皮細胞を可視化するためのFlk1-GFPおよびFlt1-tdsRed BACトランスジェニックマウスの作製 (2011)
  • Author(s): 松本健、石飛博之、浅見拓哉、伊東史子、伊東進、田中順子、三輪佳宏、高橋智、依馬正次
  • Organizer: 実験動物学会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks] 筑波大学 解剖学・発生学研究室
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks] 動脈硬化の進行を促進するたんぱく質を発見
  • URL: http://www.tsukuba.ac.jp/attention-research/p201401201900.html
• [Remarks] 解剖学・発生学研究室
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Patent(Industrial Property Rights)] テトラサイクリン系抗生物質によるタンパク質分解制御法 (2012)
  • Inventor(s): 三輪佳宏
  • Industrial Property Rights Holder: 科学技術振興機構
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2012-03-09
• [Patent(Industrial Property Rights)] 蛍光資料の蛍光の局在態様を調べる方法 (2009)
  • Inventor(s): 三輪佳宏
  • Industrial Property Rights Holder: 筑波大学
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2009-10-19