title: The Lc3-synthase gene B3gnt5 is essential to pre-implantation development of the murine embryo.
abstract: BACKGROUND
  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 beta1,3 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.
  
  
  CONCLUSIONS
  The disruption of the B3gnt5 gene in mice affected the expression of lactoseries derived GLS and possibly of protein-bound beta3GlcNAc-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.
authors.affiliation: Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Switzerland. fbiellmann@access.uzh.ch
authors.forename: Franziska
authors.initials: F
authors.lastname: Biellmann
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Hülsmeier
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhou
authors.forename: Paolo
authors.initials: P
authors.lastname: Cinelli
authors.forename: Thierry
authors.initials: T
authors.lastname: Hennet
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology; D010064:Embryo Implantation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018390:Gene Targeting; D017403:In Situ Hybridization; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D011247:Pregnancy; D011995:Recombination, Genetic
chemical_list: D017351:N-Acetylglucosaminyltransferases; C067641:lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase