Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice

TLDR

We have 4 labels present. Background: Sentences with [Background] only: two lines. Combine: "Receptor tyrosine kinases Flt-1 and Flk-1/KDR, and their ligand, the vascular endothelial growth factor (VEGF), were shown to be essential for angiogenesis in the mouse embryo by gene targeting." and "Flt-1 differs from Flk-1 in that it displays a higher affinity for VEGF but lower kinase activity, suggesting the importance of its extracellular domain." So background: "Receptor tyrosine kinases Flt-1 and Flk-1/KDR and their ligand VEGF are essential for embryonic angiogenesis, with Flt-1 having higher VEGF affinity but lower kinase activity, highlighting the role of its extracellular domain." That seems good. Purpose: The line with [Purpose, Mechanism] includes purpose and mechanism.

Abstract

Receptor tyrosine kinases Flt-1 and Flk-1/KDR, and their ligand, the vascular endothelial growth factor (VEGF), were shown to be essential for angiogenesis in the mouse embryo by gene targeting. Flk-1/KDR null mutant mice exhibited impaired endothelial and hematopoietic cell development. On the other hand, Flt-1 null mutation resulted in early embryonic death at embryonic day 8.5, showing disorganization of blood vessels, such as overgrowth of endothelial cells. Flt-1 differs from Flk-1 in that it displays a higher affinity for VEGF but lower kinase activity, suggesting the importance of its extracellular domain. To examine the biological role of Flt-1 in embryonic development and vascular formation, we deleted the kinase domain without affecting the ligand binding region. Flt-1 tyrosine kinase-deficient homozygous mice ( flt-1 TK−/− ) developed normal vessels and survived. However, VEGF-induced macrophage migration was strongly suppressed in flt-1 TK−/− mice. These results indicate that Flt-1 without tyrosine kinase domain is sufficient to allow embryonic development with normal angiogenesis, and that a receptor tyrosine kinase plays a main biological role as a ligand-binding molecule.