Vegfr3-CreER T2 mouse, a new genetic tool for targeting the lymphatic system

Angiogenesis - Tập 19 - Trang 433-445 - 2016
Ines Martinez-Corral1,2, Lukas Stanczuk2,3, Maike Frye2, Maria Helena Ulvmar2, Rodrigo Diéguez-Hurtado1,4, David Olmeda1,5, Taija Makinen2, Sagrario Ortega1
1Transgenic Mice Unit, Biotechnology Programme, Spanish National Cancer Research Centre, Madrid, Spain
2Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
3Cambridge Cancer Centre, Cambridge, UK
4Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
5Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre, Madrid, Spain

Tóm tắt

The lymphatic system is essential in many physiological and pathological processes. Still, much remains to be known about the molecular mechanisms that control its development and function and how to modulate them therapeutically. The study of these mechanisms will benefit from better controlled genetic mouse models targeting specifically lymphatic endothelial cells. Among the genes expressed predominantly in lymphatic endothelium, Vegfr3 was the first one identified and is still considered to be one of the best lymphatic markers and a key regulator of the lymphatic system. Here, we report the generation of a Vegfr3-CreER T2 knockin mouse by gene targeting in embryonic stem cells. This mouse expresses the tamoxifen-inducible CreERT2 recombinase under the endogenous transcriptional control of the Vegfr3 gene without altering its physiological expression or regulation. The Vegfr3-CreER T2 allele drives efficient recombination of floxed sequences upon tamoxifen administration specifically in Vegfr3-expressing cells, both in vitro, in primary lymphatic endothelial cells, and in vivo, at different stages of mouse embryonic development and postnatal life. Thus, our Vegfr3-CreER T2 mouse constitutes a new powerful genetic tool for lineage tracing analysis and for conditional gene manipulation in the lymphatic endothelium that will contribute to improve our current understanding of this system.

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