Cdc42, a Rho family low molecular weight G protein, has important roles in various cell functions, including cytoskeletal rearrangement, cell adhesion and cell proliferation and differentiation. To investigate the involvement of Cdc42 in the activities of vascular endothelial cells, we generated Cdc42 conditional knockout mice in which Cdc42 was time -specifically deficient in vascular endothelial cells (Cdc42 fl/fl; VE-Cad CreERT: Cdc42 cKO). When the Cdc42 gene was deleted after birth, Cdc42 cKO mice were smaller than the control mice, and died between postnatal day 8 (P8) and P10. Necropsy findings confirmed that these mice had various pathological aberrances in the vessels of most organs, such as blood flow congestion and blood cell invasion. Electron microscopic observations also revealed that capillary endothelial cells were detached from the basement membrane as well as phagocytosis of dead endothelial cells induced by macrophages. Moreover, vascular sprouting from aortic rings induced by VEGF-A was diminished in samples from the Cdc42 cKO mice because of an endothelial cell proliferation defect. These results suggest that Cdc42 in vascular endothelial cells has important roles in blood vessel formation after birth.
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