Impairment of Embryonic Cell Division and Glycosaminoglycan Biosynthesis in Glucuronyltransferase-I-deficient Mice
Impairment of Embryonic Cell Division and Glycosaminoglycan Biosynthesis in Glucuronyltransferase-I-deficient Mice
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DOI：
10.1074/jbc.m110.100941
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发表时间：
2010-04-16
影响因子：
4.8
通讯作者：
Kitagawa, Hiroshi
中科院分区：
文献类型：
--
作者：
Izumikawa, Tomomi;Kanagawa, Nao;Kitagawa, Hiroshi
我们发现，在秀丽隐杆线虫中，非硫酸化软骨素是早期发育阶段正常细胞分裂和胞质分裂所必需的，而硫酸乙酰肝素对于发育后期的胚胎形态发生至关重要。为了阐明硫酸软骨素和硫酸乙酰肝素在哺乳动物早期胚胎发生中的作用，我们通过基因打靶培育了葡萄糖醛酸转移酶-I (GlcAT-I) 敲除小鼠。 GlcAT-I 是合成硫酸软骨素和硫酸乙酰肝素所需的酶。在此，我们报道，GlcAT-I 缺失的小鼠表现出硫酸软骨素和硫酸乙酰肝素的合成显着减少，并且由于胞质分裂失败，在 8 细胞阶段之前胚胎致死率显着降低。此外，用软骨素酶ABC处理野生型2细胞胚胎对细胞分裂有显着影响，尽管许多肝素酶处理的胚胎正常发育为囊胚。综上所述，这些结果表明，哺乳动物中的硫酸软骨素与线虫中的非硫酸软骨素一样，对于胚胎细胞分裂是不可或缺的。
We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development. To clarify the roles of chondroitin sulfate and heparan sulfate in early embryogenesis in mammals, we generated glucuronyltransferase-I (GlcAT-I) knock-out mice by gene targeting. GlcAT-I is an enzyme required for the synthesis of both chondroitin sulfate and heparan sulfate. Here we report that mice with a deletion of GlcAT-I showed remarkable reduction of the synthesis of chondroitin sulfate and heparan sulfate and embryonic lethality before the 8-cell stage because of failed cytokinesis. In addition, treatment of wild-type 2-cell embryos with chondroitinase ABC had marked effects on cell division, although many heparitinase-treated embryos normally developed to blastocysts. Taken together, these results suggest that chondroitin sulfate in mammals, as with non-sulfated chondroitin in C. elegans, is indispensable for embryonic cell division.