Transgenic mouse models of angiogenesis and lymphangiogenesis

The development of transgenic technologies in mice has allowed the study of the consequences of genetic alterations on angiogenesis and lymphangiogenesis. This review summarizes the murine models currently available for studies involving the manipulation of angiogenesis and lymphangiogenesis. Abnormal embryonic vascular development, resulting from defects in the formation of a primitive vascular plexus, has been observed in mice lacking vascular endothelial growth factor, vascular endothelial growth factor receptor-1 and -2, transforming growth factor-beta, fibronectin, or vascular endothelial cadherin. Defects in the expansion and remodeling of the embryonic vasculature occur in mice deficient in Tie-1, Tie-2, or angiopoietin-1, and in mice overexpressing neuropilin or angiopoietin-2. Impaired recruitment and investment of mural cells have been observed in mice with disruption of the genes encoding platelet-derived growth factor-B, platelet-derived growth factor-B receptor, and tissue factor. Gene-targeting experiments in mice have identified the EphB/ephrinB system as a critical and rate-limiting determinant of arteriovenous differentiation during embryonic vascular development. Vascular endothelial growth factor-C is necessary for the initial sprouting and migration of lymphatic endothelial cells from embryonic veins, and mice lacking vascular endothelial growth factor-C die prenatally, whereas vascular endothelial growth factor-D is dispensable for embryonic lymphatic development.