Abstract
BackgroundGlycosphingolipids (GSL) are integral components of mammalian cell membranes that are involved in cell adhesion and cell signaling processes. GSL are subdivided into structural series, like ganglio-, lacto/neolacto-, globo- and isoglo-series, which are defined by distinct trisaccharide cores. The β1,3 N-acetylglucosaminyltransferase-V (B3gnt5) enzyme catalyzes the formation of the Lc3 structure, which is the core of lactoseries derived GSL.ResultsThe biological significance of the glycoconjugates produced by the B3gnt5 enzyme was investigated by inactivating the B3gnt5 gene in the mouse germline. The disruption of the B3gnt5 protein-coding region in mouse embryonic stem cells resulted in reduced Lc3-synthase activity, supporting its specific contribution to lactoseries derived GSL synthesis. Breeding of heterozygous mutant mice failed to produce any viable progeny homozygous for the B3gnt5-null allele. The genotypic examination of embryos from heterozygous crosses showed that the disruption of the B3gnt5 gene leads to pre-implantation lethality. This finding was compatible with the expression pattern of the B3gnt5 gene in the pre-implantation embryo as shown by in situ hybridization. The analysis of GSL profiles in embryonic stem cells heterozygous for the B3gnt5-null allele confirmed the reduced levels of lactoseries derived GSL levels and of other GSL species.ConclusionThe disruption of the B3gnt5 gene in mice affected the expression of lactoseries derived GLS and possibly of protein-bound β3GlcNAc-linked glycans, thereby demonstrating an essential contribution of these glycoconjugates in early embryonic development, and supporting the importance of these glycoconjugates in cell differentiation and adhesion processes.
Highlights
Glycosphingolipids (GSL) are integral components of mammalian cell membranes that are involved in cell adhesion and cell signaling processes
Several stem cell and differentiation markers of early embryonic development, such as the stage-specific embryonic antigens SSEA-1, -3 and -4, represent carbohydrate epitopes carried by GSL [4,5,6]
To address the functional role of the B3gnt5 gene in mouse development and physiology, we inactivated this gene by homologous recombination in mouse embryonic stem (ES) cells
Summary
Glycosphingolipids (GSL) are integral components of mammalian cell membranes that are involved in cell adhesion and cell signaling processes. GSL are subdivided into structural series, like ganglio-, lacto/neolacto-, globo- and isoglo-series, which are defined by distinct trisaccharide cores. Glycosphingolipids (GSL) represent a large family of glycoconjugates, which are found abundantly on cellular membranes. GSL are classified into different series defined by their respective core structures. The main GSL series are called ganglio-, lacto-, globo-, isoglobo-, and muco-series [1]. The functional significance of GSL is diverse since these glycoconjugates have been implicated in processes such as cell adhesion, cell migration, regulation of signaling proteins and binding of (page number not for citation purposes). The repertoire of GSL expressed by an organism is subject to changes according to cell type and developmental stage. Several stem cell and differentiation markers of early embryonic development, such as the stage-specific embryonic antigens SSEA-1, -3 and -4, represent carbohydrate epitopes carried by GSL [4,5,6]
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