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PMID: 8187759 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development.

The EMBO journal ·Vol. 13 ·No. 9 ·1994-05-01 ·Pages 2056-65

Metzler M, Gertz A, Sarkar M, Schachter H, Schrader JW, Marth JD

Abstract

Complex asparagine (N)-linked oligosaccharides appear late in phylogeny and are highly regulated in vertebrates. Variations in these structures are found on the majority of cell-surface and secreted proteins. Complex N-linked oligosaccharide biosynthesis is initiated in the Golgi apparatus by the action of Mgat-1-encoded UDP-N-acetylglucosamine:alpha-3-D- mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI). To determine if these structures govern ontogenic processes in mammals, mouse embryos were generated that lacked a functional Mgat-1 gene. Inactivation of both Mgat-1 alleles produced deficiencies in GlcNAc-TI activity and complex N-linked oligosaccharides. Embryonic lethality occurred by day 10.5, thus establishing that complex N-linked oligosaccharides are required during post-implantation development. Remarkably, embryonic development proceeded into day 9 with the differentiation of multiple cell types. Complex N-linked oligosaccharides are important for morphogenic processes as neural tube formation, vascularization and the determination of left-right body plan asymmetry were impaired in the absence of a functional Mgat-1 gene.

Related Genes
Mgat-1
MeSH Terms
Animals Asparagine/metabolism Base Sequence Carbohydrate Sequence DNA Embryo, Mammalian/blood supply,metabolism Embryonic Development/genetics Female Fetal Growth Retardation/genetics Genes, Lethal Hematopoiesis Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data Morphogenesis/genetics,physiology Mutagenesis N-Acetylglucosaminyltransferases/genetics Neural Tube Defects/genetics Oligosaccharides/metabolism Phenotype Pregnancy Stem Cells/metabolism
Chemicals
Oligosaccharides Asparagine DNA N-Acetylglucosaminyltransferases alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Metzler M
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Gertz A
Sarkar M
Schachter H
Schrader J W
Marth J D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-05-01
Pages
2056-65
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395055
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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