Defective Angiogenesis and Fatal Embryonic Hemorrhage in Mice Lacking Core 1-derived O-glycans

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2004 Jan 28

PMID 14745002

Citations 96

Authors

Lijun Xia

Tongzhong Ju

Andrew Westmuckett

Guangyu An

Lacramioara Ivanciu

J Michael McDaniel

Florea Lupu

Richard D Cummings

Rodger P McEver

Affiliations

Soon will be listed here.

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.

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