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

缺乏 b 系列酸性鞘糖脂的突变小鼠视网膜神经元变性的机制。

• 批准号: 16590243
• 负责人: FURUKAWA Keiko
• 金额: $ 2.3万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590243/
• 关键词: acidic glycosphingolipids; glycosyltransferase gene; glycosyltransferase gene defective mice; GD3; retinal tissue; electroretinogram; 酸性スフィンゴ糖脂質; 糖転換酵素遺伝子; GD3合成酵素遺伝子欠損マウス; Laser Capture microdissection; 遺伝子発現

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.

我们已经进行了糖基转移酶cDNA的分子克隆，它在神经系统中高度表达，并参与酸性鞘糖脂、神经节苷脂的合成。为了研究神经节苷脂的功能，我们建立了各种糖基转移酶基因敲除（KO）小鼠，并分析了异常表型。因此，我们已经证明复合神经节苷脂是维持神经组织的重要分子，在本研究中，我们建立了GD 3转肽酶-KO小鼠模型，并分析了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GD 3在小鼠视网膜中特异性表达，提示其具有重要的作用。结论：1. b系列神经节苷脂在小鼠视网膜中的表达：在小鼠视网膜中，GD 3、GD 1b和GT 1b在神经纤维、内网状层和内核层高表达.野生型和GD 3-KO小鼠视网膜病理结果的比较将GD 3-KO小鼠与C57 BL/6小鼠以回交方式交配后，将小鼠的眼球在甲醛中固定，并用苏木精-伊红染色，然后检查视网膜组织的异常。在GD 3-KO小鼠中，内丛状层和内核层比野生型更薄，即野生型内核层由4 × 5个细胞组成，而GD 3-KO小鼠仅由3 × 4个细胞组成. GD 3-KO小鼠的视网膜电图检查。使用野生型和GD 3-KO小鼠，检查视网膜电图，结果没有差异。缺乏这些b系列神经节苷脂的GD 3-KO小鼠在这些层结构中没有表现出明显的异常形态，但是内丛状层和内核层的厚度变薄，提示B系列神经节苷脂可能参与了内网状层和内核层的完整形成。

项目成果

Overexpressed GM1 suppresses nerve growth factor (NGF) signals by modulating the intracellular localization of NGF receptors and membrane fluidity in PC12 cells

• DOI: 10.1074/jbc.m403816200
• 发表时间: 2004-08-06
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Nishio, M;Fukumoto, S;Furukawa, K
• 通讯作者: Furukawa, K

Different response of the knockout mice lacking b-series gangliosides against botulinum and tetanus toxina.

缺乏b系列神经节苷脂的基因敲除小鼠对肉毒杆菌和破伤风毒素的不同反应。

• 发表时间: 2005
• 期刊: Biochim. Biophys. Acta. 1741
• 作者: Kitamura;M.
• 通讯作者: M.

Differential enhancing effects of α2,8-sialyltransferase on the cell proliferation and mobility.

α2,8-唾液酸转移酶增强对细胞增殖和迁移率的不同影响。

• 发表时间: 2005
• 期刊: Int.J.Oncol 26
• 作者: Nikawa;T.;Ishidoh;K.;Hirasaka;K.;Ishihara;K.;Ikemoto;M.;Kano;K.;Kominami;E.;NOnaka;I.;Ogawa;T.;Adam;G.R.;Baldwin;K.M.;Yasui;N.;Kishi;K.;Takeda;S.;Kamimura Y. et al.
• 通讯作者: Kamimura Y. et al.

Over-expressed GM1 suppresses NGF signals by modulating the intra-cellular localization of NGF receptors and membrance fluidity in PC12

过度表达的 GM1 通过调节 PC12 中 NGF 受体的细胞内定位和膜流动性来抑制 NGF 信号

• 发表时间: 2004
• 期刊: J.Biol.Chem. 279
• 作者: Nishio;Masashi. et al.
• 通讯作者: Masashi. et al.

糖鎖遺伝子研究 1.14 糖脂質糖鎖の合成に関与する転移酵素遺伝子、未来を拓く糖鎖科学

糖遗传学研究1.14 参与糖脂糖链合成的转移酶基因，开辟未来的糖科学

• 发表时间: 2005
• 作者: Fujita;H;Umezaki;Y;Imamura;K;(他9名);古川鋼一
• 通讯作者: 古川鋼一