Genetic analysis of the polymorphic carbohydrate structures of gengliasides for nerve regeration and a novel therpeutic approach

神经节苷脂的糖结构多态性起着调节作用。特别是含有α-2，8唾液酸的b系列神经节苷脂被认为在各种生物学事件中起关键作用，如粘附、毒素结合、神经突延伸、细胞生长和神经炎。为了阐明b系列神经节苷脂在体内的生理功能，我们建立了GDS合成酶基因敲除小鼠。突变小鼠的神经组织形态几乎完整，无明显的行为异常，但仍保留了所有的“O”系列结构。此外，Fas介导的淋巴细胞凋亡反应在野生型和突变小鼠之间没有差异。然而，与野生型相比，突变小鼠表现出明显减少的轴突切断的舌下神经的再生，这表明b系列神经节苷脂在神经系统的修复而不是分化和通过Fas诱导的凋亡过程中更重要。

The polymorphic carbohydrate structures of gangliosides play regulatory roles. In particular, b-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to be critical in various biological events such as adhesion, toxin binding, neurite extension, cell growth, and apoptotis. To clarify the physiological functions of b-series gangliosides in viva, we have established a gene knockout mouse of GDS syntliase. Arthough all 'o-series structures were detieted in he mutant mice, they showed an almost complete nervous tissue morphology with no apparent abnormal behavior. Moreover, no differences in Fas-mediated apoptotic reaction of lymphocytes between wild type and the mutant mice were detected. However, the mutant mice exhibited clearly 'reduced regeneration of axotomized hypoglossal nerves compared with the wild type, suggesting that b-series gangliosides are more important in the repair rather than the differentiation of the nervous system and apoptotic process induced via Fas.