Elucidation of the mechanisms underlying in the immunological abnormalities of lysosomal storage diseases

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We have previously found that the progress neurologic disease induced in SD and hex-/- mice, is associated with the production of pathogenic anti-glycolipid autoantibodies. In this study, we focused immunological abnormalities in the CNS. We employed Real-time PCR analysis to monitor gene expression in the terminal stage of hexb-/- mice and found that gene associated with the immune responses were up-regulated. B lymphocyte chemoattractant CXCL-13 was one of there up-regulated genes and is expressed specifically in the CNS. To determine the role of the CXCL-13, the cxcl-13 gene was additionally disrupted in hexb-/- mice, as it play a key role in the autoimmune disease. Clinical symptoms were improved and life spans were extended in the hexb-/-, cxcl-13-/- mice and the number of neuronal cells was also increased than hexb-/- mice. These findings suggest that the expression of CXCL-13 plays an important role in the pathogenesis of neuropathy in hexb-/- mice and therefore provides a target for novel therapies.