COMPLEX ASPARAGINE-LINKED OLIGOSACCHARIDES ARE REQUIRED FOR MORPHOGENIC EVENTS DURING POSTIMPLANTATION DEVELOPMENT
COMPLEX ASPARAGINE-LINKED OLIGOSACCHARIDES ARE REQUIRED FOR MORPHOGENIC EVENTS DURING POSTIMPLANTATION DEVELOPMENT
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DOI：
10.1002/j.1460-2075.1994.tb06480.x
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发表时间：
1994-05-01
期刊：
影响因子：
11.4
通讯作者：
MARTH, JD
中科院分区：
文献类型：
--
作者：
METZLER, M;GERTZ, A;MARTH, JD
复杂的天冬酰胺(N)连接的寡糖在系统发育中出现较晚，在脊椎动物中受到高度调控。这些结构的变异存在于大多数细胞表面和分泌的蛋白质上。在高尔基体中，复杂的N-连接低聚糖的生物合成是由编码的UDP-N-乙酰氨基葡萄糖：α-3-D-甘露糖苷-β-1，2-N-乙酰氨基葡萄糖转移酶I(GlcNAc-TI)启动的。为了确定这些结构是否控制哺乳动物的个体发生过程，产生的小鼠胚胎缺乏功能性的mGat-1基因，两个mGat-1等位基因的失活导致GlcNAc-TI活性和复杂的N-连接寡糖的缺陷。胚胎死亡发生在第10.5天，因此证实了在植入后的发育过程中需要复杂的N-连接寡糖。值得注意的是，随着多种细胞类型的分化，胚胎发育一直持续到第9天。复杂的N-连接低聚糖在形态发生过程中是重要的，因为神经管的形成、血管形成和左右身体平面不对称的确定在缺乏功能的MGAT-1基因的情况下受到损害。
Complex asparagine (N)-linked oligosaccharides appear late in phylogeny and are highly regulated in vertebrates. Variations in these structures are found on the majority of cell-surface and secreted proteins. Complex N-linked oligosaccharide biosynthesis is initiated in the Golgi apparatus by the action of Mgat-1-encoded UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI). To determine if these structures govern ontogenic processes in mammals, mouse embryos were generated that lacked a functional Mgat-1 gene, Inactivation of both Mgat-1 alleles produced deficiencies in GlcNAc-TI activity and complex N-linked oligosaccharides. Embryonic lethality occurred by day 10.5, thus establishing that complex N-linked oligosaccharides are required during post-implantation development. Remarkably, embryonic development proceeded into day 9 with the differentiation of multiple cell types. Complex N-linked oligosaccharides are important for morphogenic processes as neural tube formation, vascularization and the determination of left-right body plan asymmetry were impaired in the absence of a functional Mgat-1 gene.