Biotechnology Programme

Transgenic Mice Core Unit

Head of Unit:  Sagrario Ortega
Research highlights

The Transgenic Mice Unit has designed and created several mouse models to study the lymphatic system and its implication in tumour dissemination and metastasis. One of these models is a reporter strain in which the process of lymphatic vessel growth, or lymphangiogenesis, can be monitored, in vivo, by whole body imaging. In this knockin mouse model the fluorescent/ luminescent EGFP-Luciferase fusion reporter is expressed under the endogenous transcriptional control of the Vegfr3 gene, a classical marker expressed predominantly, and almost exclusively, in lymphatic endothelium. This genetically modified strain enables tracing and quantification of lymphangiogenesis associated to tumour growth and dissemination. The response of the lymph nodes and lymphatic vessels to metastatic tumours that spread mostly through the lymphatic network leads to an activation of Vegfr3 that can be monitored in vivo in this strain (Martínez-Corral, Olmeda et al., Proc Natl Acad Sci USA 17, 2012). We have developed this reporter strain both in an immunecompetent C57Bl6 background and also in an immune-suppressed nude background. The nude background allows the generation of xenograft models in combination with our lymphoreporter knockin allele.

In collaboration with the group of Marisol Soengas at the CNIO, our lymphoreporter mouse model has been applied to study mechanisms of melanoma metastasis leading to the discovery of Midkine as a novel potential therapeutic target for melanoma (Olmeda et al., Nature 546, 2017).

Our reporter mouse model is a powerful tool for studying lymphatic vessels in physiological and pathological contexts and, combined with different mouse models of cancer such as genetically modified strains, xenograft models, etc., constitutes a unique platform for drug discovery and preclinical assays, not only in cancer and metastasis but also in many other areas such as inflammation or cardiovascular diseases (FIGURE).