Analysis of the mechanism for neuronal degeneration and regeneration and responsible gene using the mutant mice disrupted of complex ganglioside

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We have cloned a number of glycosyltransferase cDNA, products of which are acidic glycosphingolipids (ganglioside), expressed mainly in the nerve system. We have also generated knock out (KO) mice to analyze the biological function of gangliosides. As a result, we found that complex gangliosides play an important role for survival and maintenance of the nervous system. In this study, we analyzed the genes, expression levels of which are different between the wild type and GM2/GD2 synthase gene KO mice using a comprehensive appriache DNA microarray.We analyzed the chronological alteration of phenotypes in GM2/GD2 synthase gene KO mice and found the degeneration of nervous tissues in the dorsal horn of the spinal cord. Neurological examination revealed progressive sensory dysfunction with aging. We compared the mRNA expression in the spinal cord between the wild type and 20 weeks-old male KO mice by DNA microarray. mRNA expression levels of TGTP, IFI47,IFIT1,IRF7 and IRF1 were higher in KO mice than in the wild type mice. However, the difference in the expression levels was not significant. In the future, we will investigate the relation between these interferon-induced genes and the degeneration of the nervous system, and analyze the expression levels of these genes in older mice after onset of nervous system degeneration. Furthermore, we will prepare the RNA from degenerated sites in the spinal cord then analyze the gene expression profiles in the spinal cord of the wild type and KO mice.