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

被引:36
|
作者
Biellmann, Franziska [1 ,2 ]
Huelsmeier, Andreas J. [1 ,2 ]
Zhou, Dapeng [4 ]
Cinelli, Paolo [3 ]
Hennet, Thierry [1 ,2 ]
机构
[1] Univ Zurich, Inst Physiol, CH-8006 Zurich, Switzerland
[2] Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8006 Zurich, Switzerland
[3] Univ Zurich, Inst Lab Anim Sci, CH-8006 Zurich, Switzerland
[4] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA
来源
BMC DEVELOPMENTAL BIOLOGY | 2008年 / 8卷
基金
瑞士国家科学基金会;
关键词
D O I
10.1186/1471-213X-8-109
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:10
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