Mice Expressing Only Monosialoganglioside GM3 Exhibit Lethal Audiogenic Seizures

Hiromichi Kawai, Maria Laura Allende, Ryuichi Wada, Mari Kono, Kazunori Sango, Chuxia Deng, Tsuyoshi Miyakawa, Jacqueline N. Crawley, Norbert Werth, Uwe Bierfreund, Konrad Sandhoff, Richard L. Proia

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Abstract

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 β 1,4-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.

Original languageEnglish
Pages (from-to)6885-6888
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number10
DOIs
Publication statusPublished - 09-03-2001

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kawai, H., Allende, M. L., Wada, R., Kono, M., Sango, K., Deng, C., Miyakawa, T., Crawley, J. N., Werth, N., Bierfreund, U., Sandhoff, K., & Proia, R. L. (2001). Mice Expressing Only Monosialoganglioside GM3 Exhibit Lethal Audiogenic Seizures. Journal of Biological Chemistry, 276(10), 6885-6888. https://doi.org/10.1074/jbc.C000847200