2006 Fiscal Year Final Research Report Summary
Biological roles of sulfated glycolipids and pathophysiology of their deficiency
| Project/Area Number |
14082204
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kochi University (2003-2006)
Osaka University (2002) |
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Principal Investigator |
HONKE Koichi Kochi University, School of medicine, Professor (80190263)
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| Project Period (FY) |
2002 – 2006
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| Keywords | glycolipid / knockout mouse / myelin / spermatogenesis / sulfated glycan / sulfo Lewis antigen / sulfatide / seminolipid |
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| Research Abstract |
Glycolipid sulfotransferase (CST)-knockout (KO) mice manifest neurological disorders due to myelin dysfunction and an arrest of spermatogenesis, indicating that sulfatide and seminolipid are essential for myelin formation and spermatogenesis, respectively. The adhesion between the lateral loop of myelin sheath and the axolemmma at the nodes of Ranvier is deteriorated in CST-KO mice, resulting in deterioration of clustering of sodium and potassium channels. This defect occurs not at development but at maintenance process. In CST-KO mice, terminal differentiation and morphological maturation of oligodendrocytes are enhanced, indicating that sulfatide is a key molecule for the negative regulation of oligodendrocyte terminal differentiation. Transplantation of spermatogonia from the green mouse, in which green fluorescent protein is systemically expressed, revealed that defect of CST-KO mice is not in the Sertoli cells but in the germ cells. Seminolipid is found to be expressed on the plasma membranes of spermatogonia, spermatocytes, spermatids, and spermatozoa. Moreover, CST-deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction, an experimental model of renal interstitial inflammation, indicating that sulfatide is an endogenous ligand of L-selectin. CST-KO mice were employed to raise a monoclonal antibodiy (MoAb) against sulfated glycolipids. We produced a recombinant single-chain variable-fragment (scFv) antibody based on the gene on the MoAb. Finally, we introduced the GP3ST gene, which is a member of the CST gene family, into human lung adnocarcinoma cells that highly express sialyl Lewis X antigen. As the result, the cancer cells turn to express sulfo Lewis X antigen instead of sialyl Lewis X antigen and tumor metastasis via blood vessels was suppressed by the expression of GP3ST gene.
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