Research article

The Lc3-synthase gene B3gnt5 is essential to pre-implantation development of the murine embryo

Franziska Biellmann¹ , Andreas J Hülsmeier¹ , Dapeng Zhou³ , Paolo Cinelli² and Thierry Hennet¹

¹  Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Switzerland

²  Institute of Laboratory Animal Science, University of Zürich, Switzerland

³  MD Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX 77030, USA

author email corresponding author email

BMC Developmental Biology 2008, 8:109doi:10.1186/1471-213X-8-109

Published:	12 November 2008

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 β1,3 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 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.