Journal
BMC DEVELOPMENTAL BIOLOGY
Volume 8, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1471-213X-8-109
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Funding
- Functional Genomic Center Zurich (FGCZ), Switzerland
- FGCZ
- Swiss National Science Foundation [PP00A-106756, 3100A0-116039]
- Institute of Laboratory Animal Science, University of Zurich
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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. The beta 1,3 N-acetylglucosaminyltransferase-V (B3gnt5) enzyme catalyzes the formation of the Lc3 structure, which is the core of lactoseries derived GSL. Results: The 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. Conclusion: The disruption of the B3gnt5 gene in mice affected the expression of lactoseries derived GLS and possibly of protein-bound beta 3GlcNAc-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.
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