Generations of mice for imaging of cardiovascular system

• Project/Area Number: 26290030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Ema Masatsugu 滋賀医科大学, 動物生命科学研究センター, 教授 (60359578)
• Co-Investigator(Kenkyū-buntansha): 三輪 佳宏 筑波大学, 医学医療系, 講師 (70263845)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 血管内皮細胞 / 腫瘍 / 発生 / 血管新生 / 動物

Outline of Final Research Achievements

We generated a novel transgenic (Tg) mouse that expresses a bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1 expression in endothelial cells and lymphatic endothelial cells during development and tumour growth. Importantly, bioluminescence imaging of endothelial cells from the aortic rings of Flk1-Nano-lantern BAC Tg mice enabled us to observe endothelial sprouting for 18 hr without any detectable phototoxicity. Furthermore, Flk1-Nano-lantern BAC Tg mice achieved time-lapse luminescence imaging of tumour angiogenesis in freely moving mice with implanted tumours.
We also Lrrc33 KO mice and demonstrated that Lrrc33 is important for the function of tumour endothelial cells.

Research Products

• [Journal Article] Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern Transgenic Mice. (2017)
  • Author(s): Matsushita J, Inagaki S, Nishie T, Sakasai T, Tanaka J, Watanabe C, Mizutani KI, Miwa Y, Matsumoto K, Takara K, Naito H, Kidoya H, Takakura N, Nagai T, Takahashi S, Ema M.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 46597-46597
  • DOI: 10.1038/srep46597
  • NAID: 120007129140
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Visualization of the Epiblast and Visceral Endodermal Cells Using Fgf5-P2A-Venus BAC Transgenic Mice and Epiblast Stem Cells. (2016)
  • Author(s): Khoa le TP, Azami T, Tsukiyama T, Matsushita J, Tsukiyama-Fujii S, Takahashi S, Ema M.
  • Journal Title: PLoS ONE Volume: 11 Issue: 3 Pages: e0150715-e0150715
  • DOI: 10.1371/journal.pone.0150715
  • NAID: 120007129540
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling. (2015)
  • Author(s): Hongu T, Funakoshi Y, Fukuhara S, Suzuki T, Sakimoto S, Takakura N, Ema M, Takahashi S, Itoh S, Kato M, Hasegawa H, Mochizuki N, Kanaho Y.
  • Journal Title: Nat. Commun. Volume: 6 Issue: 1 Pages: 7925-7925
  • DOI: 10.1038/ncomms8925
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus (2015)
  • Author(s): Matsuo K, Kuroda Y, Nango N, Shimoda K, Kubota Y, Ema M, Bakiri L, Wagner EF, Takeda Y, Yashiro W, Momose A
  • Journal Title: Development Volume: 142 Pages: 3912-3920
  • Peer Reviewed
• [Presentation] Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern Transgenic Mice (2016)
  • Author(s): M Ema, S Inagaki, T Nishie, T Sakasai, J Tanaka, Y Miwa, K Matsumoto, K Takara, H Naito, H Kidoya, N Takakura, T Nagai, S Takahashi, J Matsushita
  • Organizer: 血管生物医学会
  • Place of Presentation: 長崎
  • Year and Date: 2016-12-08
• [Remarks] 滋賀医科大学動物生命科学研究センター幹細胞・ヒト疾患モデル研究分野
  • URL: http://lab.rcals.jp
• [Remarks] 研究室・ホームページ
  • URL: http://lab.rcals.jp