The Lc3-synthase gene B3gnt5 is essential to pre-implantation development of the murine embryo.
The Lc3-synthase gene B3gnt5 is essential to pre-implantation development of the murine embryo.
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DOI：
10.1186/1471-213x-8-109
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发表时间：
2008-11-12
影响因子：
--
通讯作者：
Hennet T
中科院分区：
文献类型：
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作者：
Biellmann F;Hülsmeier AJ;Zhou D;Cinelli P;Hennet T
鞘糖脂（GSL）是哺乳动物细胞膜的组成部分，参与细胞粘附和细胞信号传导过程。GSL被细分为结构系列，如神经节-，乳糖/新乳糖-，globo-和isoglo-系列，其由不同的三糖核心定义。β 1，3 N-乙酰葡糖胺基转移酶-V（B3 gnt 5）催化Lc 3结构的形成，Lc 3结构是源自乳糖系列的GSL的核心。通过在小鼠生殖系中失活B3 gnt 5基因来研究由B3 gnt 5酶产生的糖缀合物的生物学意义。小鼠胚胎干细胞中B3 gnt 5蛋白编码区的破坏导致Lc 3合酶活性降低，支持其对乳系列衍生的GSL合成的特异性贡献。杂合突变小鼠的育种未能产生任何可存活的B3 gnt 5-null等位基因纯合后代。来自杂合杂交的胚胎的基因型检查表明，B3 gnt 5基因的破坏导致植入前致死。这一发现与原位杂交所示的B3 gnt 5基因在植入前胚胎中的表达模式相一致。对B3 gnt 5-无效等位基因杂合的胚胎干细胞中的GSL谱的分析证实了乳系列衍生的GSL水平和其他GSL种类的水平降低。小鼠中B3 gnt 5基因的破坏影响了乳系列衍生的GLS的表达，并可能影响了蛋白结合的β 3GlcNAc连接聚糖的表达，从而证明了这些糖缀合物在早期胚胎发育中的重要作用，并支持了这些糖缀合物在细胞分化和粘附过程中的重要性。
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. 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. 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.