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

我们进行了糖基转移酶cDNA的分子克隆，该基因在神经系统中高度表达，参与酸性鞘糖脂、神经节脂苷的合成。为了研究神经节苷的功能，我们产生了多种糖基转移酶基因敲除（KO）小鼠，并分析了异常表型。因此，我们已经证明了复杂的神经节苷是维持神经组织的必要分子。在本研究中，我们生成GD3合成酶- ko小鼠，分析b系列神经节苷脂在视网膜组织中的作用，因为神经节苷脂GD3在小鼠视网膜中特异性表达，表明其具有重要作用。研究结果如下：1。鼠视网膜b系列神经节苷的表达。在小鼠视网膜中，GD3、GD1b和GT1b在神经纤维、内丛状层和内核层中高表达。野生型与GD3-KO小鼠视网膜病理表现的比较。GD3-KO小鼠与C57BL/6小鼠背交后，用甲醛固定小鼠眼球，苏木精-伊红染色，观察视网膜组织异常。GD3-KO小鼠内丛状和内核层较野生型薄；即野生型小鼠的内核层由4 ~ 5个细胞组成，而GD3-KO小鼠只有3 ~ 4个细胞。GD3-KO小鼠视网膜电图检查。野生型和GD3-KO小鼠视网膜电图检查无差异。缺乏b系列神经节苷的GD3-KO小鼠在这些层结构中未见明显的形态异常，但内丛状层和内核层厚度变薄，提示b系列神经节苷可能参与了内丛状层和内核层的完整形成。

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.