Vegfr3-tdTomato, a reporter mouse for microscopic visualization of lymphatic vessel by multiple modalities

Lymphatic vessels are indispensable for tissue fluid homeostasis, transport of solutes and dietary lipids and immune cell trafficking. In contrast to blood vessels, which are easily visible by their erythrocyte cargo, lymphatic vessels are not readily detected in the tissue context. Their invisibili...

Verfasser: Redder, Esther
Kirschnick, Nils
Bobe, Stefanie
Hägerling, René
Hansmeier, Nils Rouven
Kiefer, Friedemann
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2021
Publikation in MIAMI:29.10.2021
Datum der letzten Änderung:17.01.2023
Angaben zur Ausgabe:[Electronic ed.]
Quelle:PLoS ONE 16 (2021) 9, e0249256, 1-21
Schlagwörter:Genetically modified animals; Mouse models; Tissue clearing; Immunostaining; Light-sheet fluorescence microscopy; Endothelial cells; Fluorescence microscopy; Thoracic diaphragm
Fachgebiet (DDC):610: Medizin und Gesundheit
Lizenz:CC BY 4.0
Sprache:English
Förderung:Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF-Dokument
URN:urn:nbn:de:hbz:6-06009523068
Weitere Identifikatoren:DOI: 10.17879/31059587862
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-06009523068
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  • Onlinezugriff:10.1371_journal_pone_0249256.pdf

    Lymphatic vessels are indispensable for tissue fluid homeostasis, transport of solutes and dietary lipids and immune cell trafficking. In contrast to blood vessels, which are easily visible by their erythrocyte cargo, lymphatic vessels are not readily detected in the tissue context. Their invisibility interferes with the analysis of the three-dimensional lymph vessel structure in large tissue volumes and hampers dynamic intravital studies on lymphatic function and pathofunction. An approach to overcome these limitations are mouse models, which express transgenic fluorescent proteins under the control of tissue-specific promotor elements. We introduce here the BAC-transgenic mouse reporter strain Vegfr3-tdTomato that expresses a membrane-tagged version of tdTomato under control of Flt4 regulatory elements. Vegfr3-tdTomato mice inherited the reporter in a mendelian fashion and showed selective and stable fluorescence in the lymphatic vessels of multiple organs tested, including lung, kidney, heart, diaphragm, intestine, mesentery, liver and dermis. In this model, tdTomato expression was sufficient for direct visualisation of lymphatic vessels by epifluorescence microscopy. Furthermore, lymph vessels were readily visualized using a number of microscopic modalities including confocal laser scanning, light sheet fluorescence and two-photon microscopy. Due to the early onset of VEGFR-3 expression in venous embryonic vessels and the short maturation time of tdTomato, this reporter offers an interesting alternative to Prox1-promoter driven lymphatic reporter mice for instance to study the developmental differentiation of venous to lymphatic endothelial cells.