Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
Copyright policy )Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
The core 1 β1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAcα1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galβ1-3GalNAcα1-Ser/Thr (T antigen). The T antigen is a precursor for extended and branched O-glycans of largely unknown function. We found that wild-type mice expressed the NeuAcα2-3Galβ1-3GalNAcα1-Ser/Thr primarily in endothelial, hematopoietic, and epithelial cells during development. Gene-targeted mice lacking T-synthase instead expressed the nonsialylated Tn antigen in these cells and developed brain hemorrhage that was uniformly fatal by embryonic day 14. T-synthase–deficient brains formed a chaotic microvascular network with distorted capillary lumens and defective association of endothelial cells with pericytes and extracellular matrix. These data reveal an unexpected requirement for core 1–derived O-glycans during angiogenesis.
- University of Oklahoma Health Sciences Ctr United States
- University of Oklahoma Health Sciences Center United States
- Oklahoma Medical Research Foundation United States
Mice, Knockout, Glycosylation, Microcirculation, Endothelial Cells, Neovascularization, Physiologic, Gestational Age, Hemorrhage, Embryo, Mammalian, Galactosyltransferases, Article, Extracellular Matrix, Mice, Polysaccharides, Pregnancy, Animals, Humans, Antigens, Tumor-Associated, Carbohydrate, Female, Antigens, Viral, Tumor, Pericytes, Blood Coagulation
Mice, Knockout, Glycosylation, Microcirculation, Endothelial Cells, Neovascularization, Physiologic, Gestational Age, Hemorrhage, Embryo, Mammalian, Galactosyltransferases, Article, Extracellular Matrix, Mice, Polysaccharides, Pregnancy, Animals, Humans, Antigens, Tumor-Associated, Carbohydrate, Female, Antigens, Viral, Tumor, Pericytes, Blood Coagulation
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