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，相互作用对于细胞生长和分化很重要。通过细胞表面碳水的相互作用是其中必不可少的机制之一。我们一直在研究碳氢化物在体内的作用，通过在β-1.4-galactosyhransferase-i（β4Galt-i）中产生基因敲除小鼠定位。最近发现β4GALT形成了由7种基因组成的基因家族，这些基因具有自己的作用。我们详细详细分析了β4Galt-I KO小鼠的碳水化物结构。 β4Galt-I基因对各种细胞类型的生物合成的贡献是通过测量β1,4-链接中的GAL保留来估计的。接下来，在β4GALT-I KO小鼠中分析了Selectins的碳氢化配体，已知由β4Galts和其他糖基转移酶合成。还估计了β4Galt-I基因对其生物合成的贡献。此外，研究了β4Galt-I KO小鼠的炎症反应和β4Galt-I缺乏症的作用。另外，研究了β4Galt-I缺乏对皮肤伤口愈合的影响。我们的结果表明，β4GALT-I在选择蛋白的碳氢化配体的生物合成中起重要作用，它们的不足导致炎症反应的减少，并延迟了β4Galt-I KO小鼠的β4Galt-i KO ko ko中的β4GALT-I KO小鼠。在胚胎发生后期致命的背景。自从斑点而不是胚胎的迟缓在死亡前几天是显着的，因此建议plapeta的缺陷是胚胎致死性的原因。由于根据遗传背景而变化的致死性的原因可能是其他β4Galts的补偿活性，因此在另一个β4Galt基因中缺乏基因基因敲除小鼠。阐明这些P4GALT基因的作用的研究正在进行中。