Fluorescence and bioluminescence imaging of angiogenesis in Flk1-Nano-lantern transgenic mice

Jun Matsushita; Shigenori Inagaki; Tomomi Nishie; Tomoki Sakasai; Junko Tanaka; Chisato Watanabe; Ken ichi Mizutani; Yoshihiro Miwa; Ken Matsumoto; Kazuhiro Takara; Hisamichi Naito; Hiroyasu Kidoya; Nobuyuki Takakura; Takeharu Nagai; Satoru Takahashi; Masatsugu Ema

doi:10.1038/srep46597

Fluorescence and bioluminescence imaging of angiogenesis in Flk1-Nano-lantern transgenic mice

Jun Matsushita, Shigenori Inagaki, Tomomi Nishie, Tomoki Sakasai, Junko Tanaka, Chisato Watanabe, Ken ichi Mizutani, Yoshihiro Miwa, Ken Matsumoto, Kazuhiro Takara, Hisamichi Naito, Hiroyasu Kidoya, Nobuyuki Takakura, Takeharu Nagai, Satoru Takahashi, Masatsugu Ema

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Abstract

Angiogenesis is important from normal development as well as from tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model from imaging. Here, we report the generation of 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 from 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. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.

Original language	English
Article number	46597
Journal	Scientific reports
Volume	7
DOIs	https://doi.org/10.1038/srep46597
Publication status	Published - 2017
Externally published	Yes

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Matsushita, J., Inagaki, S., Nishie, T., Sakasai, T., Tanaka, J., Watanabe, C., Mizutani, K. I., Miwa, Y., Matsumoto, K., Takara, K., Naito, H., Kidoya, H., Takakura, N., Nagai, T., Takahashi, S., & Ema, M. (2017). Fluorescence and bioluminescence imaging of angiogenesis in Flk1-Nano-lantern transgenic mice. Scientific reports, 7, [46597]. https://doi.org/10.1038/srep46597

@article{f23f9d97447147cda429bd6e71a10b6b,

title = "Fluorescence and bioluminescence imaging of angiogenesis in Flk1-Nano-lantern transgenic mice",

abstract = "Angiogenesis is important from normal development as well as from tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model from imaging. Here, we report the generation of 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 from 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. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.",

author = "Jun Matsushita and Shigenori Inagaki and Tomomi Nishie and Tomoki Sakasai and Junko Tanaka and Chisato Watanabe and Mizutani, {Ken ichi} and Yoshihiro Miwa and Ken Matsumoto and Kazuhiro Takara and Hisamichi Naito and Hiroyasu Kidoya and Nobuyuki Takakura and Takeharu Nagai and Satoru Takahashi and Masatsugu Ema",

note = "Funding Information: We would like to thank Ms. Yuko Hamada for her helpful assistance. This work was supported in part by a grant from PRESTO, Japan Science and Technology Agency (JST) (to M.E.), JSPS KAKENHI Grant number 26290030 (to M.E.) and “JST-SENTAN” and the MEXT Scientific Research on Innovative Areas, {\textquoteleft}Spying minority in biological phenomena{\textquoteright} (No. 3306) to T. Nagai. We also thank the Bionanophotonics Consortium (BNPC) for assistance in experiments using microscopy.",

year = "2017",

doi = "10.1038/srep46597",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Fluorescence and bioluminescence imaging of angiogenesis in Flk1-Nano-lantern transgenic mice

AU - Matsushita, Jun

AU - Inagaki, Shigenori

AU - Nishie, Tomomi

AU - Sakasai, Tomoki

AU - Tanaka, Junko

AU - Watanabe, Chisato

AU - Mizutani, Ken ichi

AU - Miwa, Yoshihiro

AU - Matsumoto, Ken

AU - Takara, Kazuhiro

AU - Naito, Hisamichi

AU - Kidoya, Hiroyasu

AU - Takakura, Nobuyuki

AU - Nagai, Takeharu

AU - Takahashi, Satoru

AU - Ema, Masatsugu

N1 - Funding Information: We would like to thank Ms. Yuko Hamada for her helpful assistance. This work was supported in part by a grant from PRESTO, Japan Science and Technology Agency (JST) (to M.E.), JSPS KAKENHI Grant number 26290030 (to M.E.) and “JST-SENTAN” and the MEXT Scientific Research on Innovative Areas, ‘Spying minority in biological phenomena’ (No. 3306) to T. Nagai. We also thank the Bionanophotonics Consortium (BNPC) for assistance in experiments using microscopy.

PY - 2017

Y1 - 2017

N2 - Angiogenesis is important from normal development as well as from tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model from imaging. Here, we report the generation of 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 from 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. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.

AB - Angiogenesis is important from normal development as well as from tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model from imaging. Here, we report the generation of 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 from 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. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.

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M1 - 46597

ER -

Fluorescence and bioluminescence imaging of angiogenesis in Flk1-Nano-lantern transgenic mice

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