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

http://www.ncbi.nlm.nih.gov/pubmed/9689083

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.

Pubmed ID: 9689083 RIS Download

Mesh terms: Animals | Base Sequence | Capillary Permeability | Cells, Cultured | DNA Primers | Embryonic and Fetal Development | Endothelial Growth Factors | Endothelium, Vascular | Gene Targeting | Lymphokines | Macrophages | Mice | Neovascularization, Physiologic | Proto-Oncogene Proteins | Receptor Protein-Tyrosine Kinases | Vascular Endothelial Growth Factor A | Vascular Endothelial Growth Factor Receptor-1 | Vascular Endothelial Growth Factors

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