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 e...

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Autores principales: Xia, Lijun, Ju, Tongzhong, Westmuckett, Andrew, An, Guangyu, Ivanciu, Lacramioara, McDaniel, J. Michael, Lupu, Florea, Cummings, Richard D., McEver, Rodger P.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172228/
https://www.ncbi.nlm.nih.gov/pubmed/14745002
http://dx.doi.org/10.1083/jcb.200311112
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author Xia, Lijun
Ju, Tongzhong
Westmuckett, Andrew
An, Guangyu
Ivanciu, Lacramioara
McDaniel, J. Michael
Lupu, Florea
Cummings, Richard D.
McEver, Rodger P.
author_facet Xia, Lijun
Ju, Tongzhong
Westmuckett, Andrew
An, Guangyu
Ivanciu, Lacramioara
McDaniel, J. Michael
Lupu, Florea
Cummings, Richard D.
McEver, Rodger P.
author_sort Xia, Lijun
collection PubMed
description 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.
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spelling pubmed-21722282008-03-05 Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans Xia, Lijun Ju, Tongzhong Westmuckett, Andrew An, Guangyu Ivanciu, Lacramioara McDaniel, J. Michael Lupu, Florea Cummings, Richard D. McEver, Rodger P. J Cell Biol Article 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. The Rockefeller University Press 2004-02-02 /pmc/articles/PMC2172228/ /pubmed/14745002 http://dx.doi.org/10.1083/jcb.200311112 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Xia, Lijun
Ju, Tongzhong
Westmuckett, Andrew
An, Guangyu
Ivanciu, Lacramioara
McDaniel, J. Michael
Lupu, Florea
Cummings, Richard D.
McEver, Rodger P.
Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
title Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
title_full Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
title_fullStr Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
title_full_unstemmed Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
title_short Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans
title_sort defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived o-glycans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172228/
https://www.ncbi.nlm.nih.gov/pubmed/14745002
http://dx.doi.org/10.1083/jcb.200311112
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