Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions.
Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions.
复制标题
神经节苷脂合成的中断会导致中枢神经系统变性并改变轴突-神经胶质相互作用。
DOI：
10.1073/pnas.0407785102
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发表时间：
2005
影响因子：
11.1
通讯作者：
Proia,RichardL
中科院分区：
文献类型：
--
作者：
Yamashita,Tadashi;Wu,Yun-Ping;Sandhoff,Roger;Werth,Norbert;Mizukami,Hiroki;Ellis,JessicaM;Dupree,JeffreyL;Geyer,Rudolf;Sandhoff,Konrad;Proia,RichardL
神经节苷脂是唾液酸化鞘糖脂，是神经元上的主要糖复合物，在中枢神经系统 (CNS) 中携带大部分唾液酸。为了确定神经节苷脂合成在中枢神经系统内的作用，生成了两个关键神经节苷脂特异性糖基转移酶基因 Siat9（编码 GM3 合酶）和 Galgt1（编码 GM2 合酶）携带无效突变的小鼠。这些双无效小鼠无法合成鞘糖脂神经节系列的神经节苷脂，这是中枢神经系统中主要的神经节苷脂类别。断奶后不久，存活的小鼠患上了严重的神经退行性疾病，导致死亡。组织病理学检查显示中枢神经系统白质区域存在显着的空泡病理，伴有轴突变性和轴突-神经胶质相互作用受到干扰。这些结果表明，神经节苷脂合成对于稳定的中枢神经系统的发育至关重要，可能是通过促进轴突和神经胶质细胞之间的相互作用来实现的。
Gangliosides, which are sialylated glycosphingolipids, are the major class of glycoconjugates on neurons and carry the majority of the sialic acid within the central nervous system (CNS). To determine the role of ganglioside synthesis within the CNS, mice carrying null mutations in two critical ganglioside-specific glycosyltransferase genes,Siat9(encoding GM3 synthase) andGalgt1(encoding GM2 synthase), were generated. These double-null mice were unable to synthesize gangliosides of the ganglio-series of glycosphingolipids, which are the major ganglioside class in the CNS. Soon after weaning, viable mice developed a severe neurodegenerative disease that resulted in death. Histopathological examination revealed striking vacuolar pathology in the white matter regions of the CNS with axonal degeneration and perturbed axon–glia interactions. These results indicate that ganglioside synthesis is essential for the development of a stable CNS, possibly by means of the promotion of interactions between axon and glia.