Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 16, Pages 6223-6228Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1115542109
Keywords
bioluminescence; fluorescence; knockin mouse
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Funding
- Ministry of Science and Innovation of Spain [BIO2009-09488, BIO2006-03213]
- Spanish National Cancer Research Centre (CNIO) Transgenesis, Comparative Pathology, Confocal Microscopy, Molecular Imaging, and Animal Facility Core Units
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Lymphatic vessel growth or lymphangiogenesis occurs during embryonic development and wound healing and plays an important role in tumor metastasis and inflammatory diseases. However, the possibility of noninvasive detection and quantification of lymphangiogenesis has been lacking. Here, we present the Vegfr3(EGFPLuc) mouse model, where an EGFP-luciferase fusion protein, expressed under the endogenous transcriptional control of the Vegfr3 gene, allows the monitoring of physiological and pathological lymphangiogenesis in vivo. We show tracking of lymphatic vessel development during embryogenesis as well as lymphangiogenesis induced by specific growth factors, during wound healing and in contact hypersensitivity (CHS) - induced inflammation where we also monitor down-regulation of lymphangiogenesis by the glucocorticoid dexamethasone. Importantly, the Vegfr3-reporter allowed us to tracking tumor-induced lymphangiogenesis at the tumor periphery and in lymph nodes in association with the metastatic process. This is the first reporter mouse model for luminescence imaging of lymphangiogenesis. It should provide an important tool for studying the involvement of lymphangiogenesis in pathological processes.
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