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Published online 26 January 2004. doi:10.1083/jcb.200311112
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 3, 451-459
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Article

Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans



Lijun Xia1, Tongzhong Ju2, Andrew Westmuckett1, Guangyu An1, Lacramioara Ivanciu1, J. Michael McDaniel1, Florea Lupu1, Richard D. Cummings2,3, and Rodger P. McEver1,2,3

1 Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 2 Department of Biochemistry and Molecular Biology, and 3 Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

Address correspondence to Lijun Xia or Rodger P. McEver, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th St., Oklahoma City, OK 73104. Tel.: (405) 271-6480. Fax: (405) 271-3137. email: lijun-xia{at}omrf.ouhsc.edu; rodger-mcever{at}omrf.ouhsc.edu

The core 1 ß1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAc{alpha}1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galß1-3GalNAc{alpha}1-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 NeuAc{alpha}2-3Galß1-3GalNAc{alpha}1-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.

Key Words: T-synthase; endothelial cell; galactosyltransferase; mucin; development

The online version of this article contains supplemental material.

Abbreviations used in this paper: HPA, Helix pomatia agglutinin; MAG, myelin-associated glycoprotein; PNA, Arachis hypogaea agglutinin; sialyl-T antigen, NeuAc{alpha}2-3Galß1-3GalNAc{alpha}1-Ser/Thr; sialyl-Tn antigen, NeuAc{alpha}2-6GalNAc{alpha}1-Ser/Thr; T antigen, Galß1-3GalNAc{alpha}1-Ser/Thr; Tn antigen, GalNAc{alpha}1-Ser/Thr; T-synthase, core 1 ß1-3-galactosyltransferase.


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