Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures
Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures
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DOI：
10.1074/jbc.c000847200
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发表时间：
2001-03-09
影响因子：
4.8
通讯作者：
Proia, RL
中科院分区：
文献类型：
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作者：
Kawai, H;Allende, ML;Proia, RL
神经节苷脂是一类含有唾液酸的鞘糖脂。虽然它们在神经元细胞膜上丰富，但它们在中枢神经系统（CNS）中的确切功能和重要性在很大程度上仍不清楚。我们已经破坏了编码GD 3合酶（GD 3S）的基因，GD 3S是一种在CNS中表达的唾液酸转移酶，负责合成b系列神经节苷脂。GD 3S-/-小鼠，即使没有b系列神经节苷脂，似乎经历正常的发育，并具有正常的寿命。为了进一步限制神经节苷脂的表达，GD 3S突变小鼠与携带编码β 1，4-N-乙酰氨基半乳糖转移酶的破坏的GalNAcT基因的小鼠杂交。这些双突变小鼠表达GM 3作为其主要的神经节苷脂。与单突变小鼠相比，双突变小鼠表现出猝死表型，并且对声音刺激诱导的致死性癫痫发作极其敏感。这些结果明确表明，神经节苷脂在中枢神经系统的正常功能中发挥着重要作用。
Gangliosides are a family of glycosphingolipids that contain sialic acid. Although they are abundant on neuronal cell membranes, their precise functions and importance in the central nervous system (CNS) remain largely undefined. We have disrupted the gene encoding GD3 synthase (GD3S), a sialyltransferase expressed in the CNS that is responsible for the synthesis of b-series gangliosides. GD3S-/- mice, even with an absence of b-series gangliosides, appear to undergo normal development and have a normal life span. To further restrict the expression of gangliosides, the GD3S mutant mice were crossbred with mice carrying a disrupted GalNAcT gene encoding beta1,4-N-acetylgalactosaminyltransferase. These double mutant mice expressed GM3 as their major ganglioside. In contrast to the single mutant mice, the double mutants displayed a sudden death phenotype and were extremely susceptible to induction of lethal seizures by sound stimulus. These results demonstrate unequivocally that gangliosides play an essential role in the proper functioning of the CNS.