Elucidation of individual roles of the galactosyl|ransferase gene family using gene knockout mice

使用基因敲除小鼠阐明半乳糖基|转移酶基因家族的个体作用

基本信息

批准号：
13480280
负责人：
ASANO Masahide
金额：
$ 9.54万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Cell-to-cell, interactions are important for cell growth and differentiation. The interaction through cell surface carbohydrates is one of indispensable mechanisms among them. We have been studying on the role of carbohydrates in vivo by generating a gene knockout mouse deficient in β-1.4-galactosyhransferase-I(β4GalT-I). β4GalTs are recently found to form the gene family consisting of 7 genes, which have their own roles.We analyzed carbohydrate structures of β4GalT-I KO mice in detail. Contribution of β4GalT-I gene to the biosynthesis of carbohydrates of various cell types was estimated by measuring Gal residues in the β1,4-linkage. Next, carbohydrate ligands of selectins, which are known to be synthesized by β4GalTs and other glycosyltransferases, were analyzed in β4GalT-I KO mice. Contribution of β4GalT-I gene to their biosynthesis was also estimated. Furthermore, Inflammatory responses of β4GalT-I KO mice and the effect of β4GalT-I deficiency were examined. In addition, the effect of β4GalT-I deficiency on skin wound healing was examined. Our results indicated that β4GalT-I plays an important role in the biosynthesis of carbohydrate ligands of selectins and their deficiency results in reduction of inflammatory responses and delayed wound healing in β4GalT-I KO mice.While these results were obtained using β4GalT-I KO mice on mixed genetic backgrounds, we found β4GalT-I KO mice on inbred background to be lethal during late embryogenesis. Since growth retardation of the placenta rather than the embryo was remarkable several days before its death, the defect of placenta was suggested to be a cause of the embryonic lethality. Since the reason of changeable lethality depending on genetic background might be a compensatory activity by other β4GalTs, gene knockout mice deficient in another β4GalT gene were generated. Studies on elucidating the role of these p4GalT genes are in progress.

细胞到细胞的细胞细胞细胞细胞细胞细胞中，我们一直在研究碳水化合物在体内的作用。 β4galt-I KO小鼠的碳水化合物结构详细介绍了β4Galt-I基因对各种细胞类型的碳水化合物的生物合成。通过β4GALTS和其他糖基转囊合成，在β4Galt-I KO小鼠中分析了β4Galt-I基因对其生物合成的贡献。伤口愈合。我们的β4Galt-I在Selectins的碳水化合物配体的生物合成中起着重要作用。背景，我们在胚胎发生期间在胎盘发生期间是致命的，而不是胚胎，而不是胚胎是在其死亡之前的几天是非常出色的产生了另一个β4GALT基因的缺乏。