MICE LACKING N-ACETYLGLUCOSAMINYLTRANSFERASE-I ACTIVITY DIE AT MIDGESTATION, REVEALING AN ESSENTIAL ROLE FOR COMPLEX OR HYBRID N-LINKED CARBOHYDRATES
MICE LACKING N-ACETYLGLUCOSAMINYLTRANSFERASE-I ACTIVITY DIE AT MIDGESTATION, REVEALING AN ESSENTIAL ROLE FOR COMPLEX OR HYBRID N-LINKED CARBOHYDRATES
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DOI：
10.1073/pnas.91.2.728
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发表时间：
1994-01-18
影响因子：
11.1
通讯作者：
STANLEY, P
中科院分区：
文献类型：
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作者：
IOFFE, E;STANLEY, P
真核细胞需要n链碳水化合物才能生存。然而，生物合成中间体Man5GlcNAc2Asn代替成熟的n -连接结构，使糖蛋白合成和体细胞生长正常进行。为了确定在复杂的生物学情况下是否同样正确，在胚胎干细胞中通过同源重组破坏基因mgt -1并将其传递给种系。mga1基因编码n -乙酰氨基葡萄糖转移酶I [GlcNAc-TI；alpha -, 3-mannosyl-glycoprotein beta 1, 2-N-acetylglucosaminyltransferase;糖蛋白(n -乙酰基- d -葡萄糖胺转α - d -甘露糖基-1,3-(R(1))- β - d -甘露糖基-R(2)) - β -1,2- n -乙酰基- d -葡萄糖氨基基转移酶，EC 2.4.1.101)，该转移酶启动从Man5GlcNAc2Asn合成杂化和复杂的n链碳水化合物。缺乏GlcNAc-TI活性的小鼠不能存活至足月。胚胎在妊娠8.5 ~ 13.5 d的生化和形态学分析表明，Mgat-1（-/-）胚胎发育迟缓，以神经组织发育最为明显，在发育9.5 ~ 10.5 d时死亡。
Eukaryotic cells require N-linked carbohydrates for survival. However, the biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures, allows glycoprotein synthesis and somatic cell growth to proceed normally. To determine whether the same would be true in a complex biological situation, the gene Mgat-1 was disrupted by homologous recombination in embryonic stem cells and transmitted to the germ line. The Mgat-1 gene encodes N-acetylglucosaminyltransferase I [GlcNAc-TI; alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase; UDP-N-acetyl-D-glucosamine:glycoprotein (N-acetyl-D-glucosamine to alpha-D-mannosyl-1,3-(R(1))-beta-D-mannosyl-R(2)) beta-1,2-N-acetyl-D-glucosaminyltransferase, EC 2.4.1.101], the transferase that initiates synthesis of hybrid and complex N-linked carbohydrates from Man5GlcNAc2Asn. Mice lacking GlcNAc-TI activity did not survive to term. Biochemical and morphological analyses of embryos from 8.5 to 13.5 days of gestation showed that Mgat-1(-/-) embryos are developmentally retarded, most noticeably in neural tissue, and die between 9.5 and 10.5 days of development.