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Prox1-GFP/Flt1-DsRed transgenic mice: an animal model for simultaneous live imaging of angiogenesis and lymphangiogenesis

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Abstract

The roles of angiogenesis in development, health, and disease have been studied extensively; however, the studies related to lymphatic system are limited due to the difficulty in observing colorless lymphatic vessels. But recently, with the improved technique, the relative importance of the lymphatic system is just being revealed. We bred transgenic mice in which lymphatic endothelial cells express GFP (Prox1-GFP) with mice in which vascular endothelial cells express DsRed (Flt1-DsRed) to generate Prox1-GFP/Flt1-DsRed (PGFD) mice. The inherent fluorescence of blood and lymphatic vessels allows for direct visualization of blood and lymphatic vessels in various organs via confocal and two-photon microscopy and the formation, branching, and regression of both vessel types in the same live mouse cornea throughout an experimental time course. PGFD mice were bred with CDh5CreERT2 and VEGFR2lox knockout mice to examine specific knockouts. These studies showed a novel role for vascular endothelial cell VEGFR2 in regulating VEGFC-induced corneal lymphangiogenesis. Conditional deletion of vascular endothelial VEGFR2 abolished VEGFA- and VEGFC-induced corneal lymphangiogenesis. These results demonstrate the potential use of the PGFD mouse as a powerful animal model for studying angiogenesis and lymphangiogenesis.

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Acknowledgements

This work was supported by grants from the National Institutes of Health [EY10101 (D.T.A.), EY021886, I01 BX002386 (J.H.C), and EY01792 and EY027912 (MIR)], Eversight Midwest Eye Bank Fund (J.H.C) and an unrestricted grant from Research to Prevent Blindness, New York, NY. This work made use of instruments in the Core Imaging Facility (Research Resources Center, UIC).

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA

    Wei Zhong, Xinbo Gao, Shuangyong Wang, Kyuyeon Han, Mark I. Rosenblatt, Jin-Hong Chang & Dimitri T. Azar

  2. Department of Ophthalmology, China-Japan Union Hospital, Jilin University, Changchun, 130033, Jilin, People’s Republic of China

    Wei Zhong

  3. School of Life Sciences, Jilin University, Changchun, People’s Republic of China

    Wei Zhong

  4. Department of Stem Cells and Human Disease Models, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, Japan

    Masatsugu Ema

  5. Department of Tissue Morphogenesis, Faculty of Medicine, Max-Planck-Institute for Molecular Biomedicine, University of Münster, 48149, Münster, Germany

    Susanne Adams & Ralf H. Adams

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  1. Wei Zhong
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  2. Xinbo Gao
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Contributions

WZ, XG, and SW performed experiments and data analyses. SA and RHA provide CDh5CreERT2 mice and technical support. ME provided the Flt1-DsRed mice. KH, MIR, J-HC, and DTA planned the research, discussed the data analysis, and wrote the manuscript.

Corresponding authors

Correspondence to Jin-Hong Chang or Dimitri T. Azar.

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The authors declare that they have no competing financial interests.

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Zhong, W., Gao, X., Wang, S. et al. Prox1-GFP/Flt1-DsRed transgenic mice: an animal model for simultaneous live imaging of angiogenesis and lymphangiogenesis. Angiogenesis 20, 581–598 (2017). https://doi.org/10.1007/s10456-017-9572-7

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  • DOI: https://doi.org/10.1007/s10456-017-9572-7

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