The mechanisms for the neuronal degeneration in the retina of the mutant mice lacking b-series acidic glycosphingolipids.

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We have performed molecular cloning of glycosyl transferase cDNA which are highly expressed in the nervous systems and are involved in the synthesis of acidic glycosphingolipids, gangliosides. In order to investigate the function of gangliosides, we have generated knock-out(KO) mice of various glycosyltransferase genes, and analyzed the abnormal phenotypes. Consequently, we have demonstrated that complex gangliosides were essential molecules in the maintenance of the nerve tissues.In the present study, we generated GD3 synthase-KO mice and analyzed the role of b-series gangliosides in the retina tissues, since ganglioside GD3 is specifically expressed in murine retina suggesting into important roles.The results were as follows,1. Expression of b-series gangliosides in the murin retina.In murine retina, GD3, GD1b and GT1b were highly expressed in the neurofibers, inner plexiform layer and inner nuclear layer.2. Comparison of pathological findings in the retina between the wild type and GD3-KO mice.After mating GD3-KO mice with C57BL/6 mice as a back cross manner, eye balles of the mice were fixed in formaldehyde, and stained with Hematoxylin-Eosin, then abnormalities in the retinal tissues were examined. In the GD3-KO mice, inner plexiform and inner nuclear layer were thinner than those in the wild type ; i.e. inner nuclear layer consisted of 4〜5 cells in the wild type, but just 3〜4 cells in the GD3-KO mice.3. Examination of electroretinogram in GD3-KO mice.Using the wild type and GD3-KO mice, electroretinogram was examined, resulting in no differences.The GD3-KO mice lacking these b-series ganglioside showed no apparent abnormal morphology in these layer structures, but the thickness of the inner plexiform and inner nuclear layer became thin, suggesting that b-series gangliosides may be involved in the intact formation of the inner plexiform and inner nuclear layers.