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

被引：147

作者：

Xia, LJ ^{[1
]}

Ju, TZ ^{[1
]}

Westmuckett, A ^{[1
]}

An, GY ^{[1
]}

Ivanciu, L ^{[1
]}

McDaniel, JM ^{[1
]}

Lupu, F ^{[1
]}

Cummings, RD ^{[1
]}

McEver, RP ^{[1
]}

机构：

[1] Univ Oklahoma, Cardiovasc Biol Res Program, Oklahoma Med Res Fdn, Hlth Sci Ctr, Oklahoma City, OK 73104 USA

来源：

JOURNAL OF CELL BIOLOGY | 2004年 / 164卷 / 03期

关键词：

T-synthase; endothelial cell; galactosyltransferase; mucin; development;

D O I：

10.1083/jcb.200311112

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：451 / 459

页数：9

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[11] CD8 binding to MHC class I molecules is influenced by maturation and T cell glycosylation [J].