Abstract
The core 1 beta1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAcalpha1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galbeta1-3GalNAcalpha1-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 NeuAcalpha2-3Galbeta1-3GalNAcalpha1-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.
Copyright The Rockefeller University Press
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Tumor-Associated, Carbohydrate / genetics
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Antigens, Tumor-Associated, Carbohydrate / metabolism
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Antigens, Viral, Tumor / chemistry
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Antigens, Viral, Tumor / metabolism*
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Blood Coagulation / physiology
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Embryo, Mammalian / anatomy & histology
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Embryo, Mammalian / pathology*
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Embryo, Mammalian / physiology
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Endothelial Cells / metabolism
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Extracellular Matrix
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Female
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Galactosyltransferases / genetics
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Galactosyltransferases / metabolism
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Gestational Age
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Glycosylation
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Hemorrhage*
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Humans
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Mice
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Mice, Knockout
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Microcirculation / anatomy & histology
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Microcirculation / metabolism
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Neovascularization, Physiologic*
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Pericytes / metabolism
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Polysaccharides / chemistry
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Polysaccharides / metabolism*
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Pregnancy
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Tissue Distribution
Substances
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Antigens, Tumor-Associated, Carbohydrate
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Antigens, Viral, Tumor
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Polysaccharides
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Tn antigen
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Galactosyltransferases