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

共 45 条

[1] Tn-syndrome [J].

Berger, EG .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1999, 1455 (2-3) :255-268

[2] Sialoside specificity of the siglec family assessed using novel multivalent probes - Identification of potent inhibitors of myelin-associated glycoprotein [J].

Blixt, O ;

Collins, BE ;

van den Nieuwenhof, IM ;

Crocker, PR ;

Paulson, JC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (33) :31007-31019

[3] Pathways of O-glycan biosynthesis in cancer cells [J].

Brockhausen, I .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1999, 1473 (01) :67-95

[4] Enzymatic basis for sialyl-Tn expression in human colon cancer cells [J].

Brockhausen, I ;

Yang, J ;

Dickinson, N ;

Ogata, S ;

Itzkowitz, SH .

GLYCOCONJUGATE JOURNAL, 1998, 15 (06) :595-603

[5] Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation [J].

Bugge, TH ;

Xiao, Q ;

Kombrinck, KW ;

Flick, MJ ;

Holmback, K ;

Danton, HJS ;

Colbert, MC ;

Witte, DP ;

Fujikawa, K ;

Davie, EW ;

Degen, JL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (13) :6258-6263

[6] Role of tissue factor in embryonic blood vessel development [J].

Carmeliet, P ;

Mackman, N ;

Moons, L ;

Luther, T ;

Gressens, P ;

VanVlaenderen, I ;

Demunck, H ;

Kasper, M ;

Breier, G ;

Evrard, P ;

Muller, M ;

Risau, W ;

Edgington, T ;

Collen, D .

NATURE, 1996, 383 (6595) :73-75

[7] Angiogenesis in health and disease [J].

Carmeliet, P .

NATURE MEDICINE, 2003, 9 (06) :653-660

[8] Role of the thrombin receptor In development and evidence for a second receptor [J].

Connolly, AJ ;

Ishihara, H ;

Kahn, ML ;

Farese, RV ;

Coughlin, SR .

NATURE, 1996, 381 (6582) :516-519

[9] Siglecs: sialic-acid-binding immunoglobulin-like lectins in cell-cell interactions and signalling [J].

Crocker, PR .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2002, 12 (05) :609-615

[10] Fatal haemorrhage and incomplete block to embryogenesis in mice locking coagulation factor V [J].

Cui, JS ;

OShea, KS ;

Purkayastha, A ;

Saunders, TL ;

Ginsburg, D .

NATURE, 1996, 384 (6604) :66-68

← 1 2 3 4 5 →