The lymphatic system maintains tissue homeostasis by draining fluid from peripheral tissues to the circulation. It is also important for the absorption of lipids from the gastrointestinal tract and for immune cell trafficking during inflammation. Lymphatic dysfunction may lead to lymph edema, impaired immunity and accumulation of subcutaneous fat. The lymphatic system is also the primary route for tumor cell dissemination and therefore plays an important role in cancer metastasis. TWS119 601514-19-6 development of the lymphatic vasculature begins at embryonic day 9.5–10.5 in mice, after the establishment of a functional blood vasculature. Distinct populations of cardinal vein endothelial cells positive for vascular endothelial growth factor receptor 3, the lymphatic vessel hyaluronan receptor1, and the transcription factors SOX18 and PROX1, commit to the lymphatic lineage and sprout to form lymph sacs in response to VEGF-C. Lymphatic endothelial cells begin to express podoplanin. Lymphatic vessels are formed by sprouting from the lymph sacs and are subsequently remodeled into a lymphatic vascular network consisting of blind-ended lymphatic capillaries with specialized button-type junctions, supporting influx of fluid and cells. Collecting lymphatic vessels also acquire luminal valves supporting transport of lymph without backflow. EphrinB2, angiopoietin-2 and the transcription factor FOXC2 are important for remodeling of the lymphatic vasculature. FOXC2 cooperates with the nuclear factor of activated T cells -1 downstream of VEGFR-3 to control the expression of a set of genes required for the differentiation of lymphatic vessels but is downregulated during maturation of collecting lymphatic vessels, leading to decreased expression of PROX1, VEGFR-3 and LYVE-1 at later stages. The lymphatic vasculature develops and matures during the postnatal period and in adult tissues, growth of lymphatic vessels is normally restricted to pathological conditions characterized by tissue remodeling, such as cancer and chronic inflammation. We wanted to elucidate whether CAR could play a role in development of the lymphatic system in the mouse. To study this we generated tamoxifen-inducible CAR deficient mice, which allowed us to delete Cxadr at different time points after E11, when CAR expression in cardiomyocytes was not essential for heart development. The results demonstrate an essential role of CAR for the development of the lymphatic vasculature. The aim of this study was to analyze the role of CAR in embryo development after E11.5. For this purpose we constructed a conditional knockout mouse strain, in which the CAR gene was deleted in all embryonic tissues following intraperitoneal administration of tamoxifen to pregnant females. We found that deletion of the CAR gene from E12.5, at a time point when CAR is no longer essential for cardiac development, caused subcutaneous edema, hemorrhage, and embryonic death. This suggested that CAR was important for the development of additional parts of the cardiovascular system.