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

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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.