A few examples of mouse and human genetic defects in glycosylation

Glycan classEnzyme/gene (species)Location in pathwayPhenotype
N-glycansphosphomannose isomerase MPI (human)pre-ER assembly of lipid- linked N-glycan precursorscongenital disorder of glycosylation type Ib (CDG-Ib); hepatic fibrosis; hypo- glycemia; protein-losing enteropathy; coagulopathy; treatable with oral mannose
N-glycansGlcNAcT-I Mgat1 (mouse)proximal aspect of post-ER elongationembryonic lethality (E9.5); defective vascularization; defective neural tube formation; situs inversus of the heart
N-glycansGlcNAcT-V Mgat5 (mouse)distal aspect of post-ER elongationautoimmune kidney disease; hyperactive T-cell receptor signaling; defective maternal nurturing behavior; reduced tumorigenesis of mammary epithelium
O-glycanscore 2 GlcNAcT-I C2gnt1 (mouse)core 2 branch of GalNAc- linked O-glycansdefective leukocyte P- and L-selectin ligand activity
O-glycanspolypeptide O-fucosyltransferase I Pofut1 (mouse)serine and threonine O-fucosylationembryonic lethality (E9.5); defects that phenocopy Notch nullizygosity; defective vasculogenesis, neurogenesis; cardiogenesis; somito genesis
GlycosphingolipidsUDP-galactose: ceramide Gal-T Cgt (mouse)galactosylation of ceramideloss of galactocerebrosides in peripheral nerve myelin; nerve conduction defects, tremor and death from ataxia; loss of sympathetic nervous-system-dependent egress of hematopoietic stem and progenitor cells from bone marrow
Shared outer sequencesβ1-4galactosyltransferase-1 GalT1 (mouse)outer-chain galactosylation of N- and O-glycansdefective growth; faulty differentiation of epithelia; endocrine insufficiency
Sialic acidsST3Gal-I ST3Gal1 (mouse)α2-3 sialylation of core 1 O-glycansenhanced CD8αβ binding avidity to MHC class I molecules; proapoptotic phenotype in CD8+ lymphocytes
Glycophospholipid anchorsGlcNAc phosphatidylinositol synthetase PIG-A (mouse, human)synthesis of the first intermediate in GPI anchor formationgerm-line knockout embryonic lethal in mice; somatic knockout in hematopoietic stem cells removes complement- regulating molecules CD59 and DAF and results in enhanced complement- mediated red cell lysis (called paroxysmal nocturnal hemoglobinuria in humans)
Hyaluronanhyaluronan synthetase 2 Has2 (mouse)synthesis of hyaluronanembryonic lethality (E9.5–E10); absence of cardiac endothelial transformation to mesenchyme; deficiency in formation of the atrioventricular canal
Sulfated glycos- aminoglycansglucosaminyl N-deacetylase/ N-sulfotransferase-1 Ndst1 (mouse)synthesis of heparan sulfateperinatal lethality due to brain/skull defects and lung surfactant problems
Sulfated glycos- aminoglycansglucosaminyl N-deacetylase/ N-sulfotransferase-2 Ndst2 (mouse)synthesis of heparan sulfateloss of heparin sulfate from mast cells; defective granule formation in mast cells
O-GlcNAc modificationO-GlcNAc transferase Ogt (mouse)GlcNAc addition to serines and threonines on nuclear and cytoplasmic proteinshemizygosity for this X-linked locus is not compatible even with cellular viability of the targeted embryonic stem cell

From: Chapter 6, Biological Roles of Glycans

Cover of Essentials of Glycobiology
Essentials of Glycobiology. 2nd edition.
Varki A, Cummings RD, Esko JD, et al., editors.
Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2009.
Copyright © 2009, The Consortium of Glycobiology Editors, La Jolla, California.

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