THE RECEPTOR TYROSINE KINASE TIE IS REQUIRED FOR INTEGRITY AND SURVIVAL OF VASCULAR ENDOTHELIAL-CELLS

Vascular endothelial cells are critical for the development and functi on of the mammalian circulatory system, We have analyzed the role of t he endothelial cell-specific receptor tyrosine kinase TIE in the mouse vasculature, Mouse embryos homozygous for a disrupted Tie allele deve loped severe edema, their microvasculature was ruptured and they died between days 13.5 and 14.5 of gestation, The major blood vessels of th e homozygous embryos appeared normal, Cells lacking a functional Tie g ene were unable to contribute to the adult kidney endothelium in chime ric animals, further demonstrating the intrinsic requirement for TIE i n endothelial cells, We conclude that TIE is required during embryonic development for the integrity and survival of vascular endothelial ce lls, particularly in the regions undergoing angiogenic growth of capil laries, TIE is not essential, however for vasculogenesis, the early di fferentiation of endothelial cells.