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

Research output: Contribution to journalArticle

185 Citations (Scopus)

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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Gangliosides
Seizures
Neurology
Gene encoding
Central Nervous System
N-Acetylgalactosaminyltransferases
Sialyltransferases
Glycosphingolipids
N-Acetylneuraminic Acid
Cell membranes
Sudden Death
Genes
sialogangliosides
Acoustic waves
Cell Membrane
Phenotype

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., ... 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
Kawai, Hiromichi ; Allende, Maria Laura ; Wada, Ryuichi ; Kono, Mari ; Sango, Kazunori ; Deng, Chuxia ; Miyakawa, Tsuyoshi ; Crawley, Jacqueline N. ; Werth, Norbert ; Bierfreund, Uwe ; Sandhoff, Konrad ; Proia, Richard L. / Mice Expressing Only Monosialoganglioside GM3 Exhibit Lethal Audiogenic Seizures. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 10. pp. 6885-6888.
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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.",
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Kawai, H, Allende, ML, Wada, R, Kono, M, Sango, K, Deng, C, Miyakawa, T, Crawley, JN, Werth, N, Bierfreund, U, Sandhoff, K & Proia, RL 2001, 'Mice Expressing Only Monosialoganglioside GM3 Exhibit Lethal Audiogenic Seizures', Journal of Biological Chemistry, vol. 276, no. 10, pp. 6885-6888. https://doi.org/10.1074/jbc.C000847200

Mice Expressing Only Monosialoganglioside GM3 Exhibit Lethal Audiogenic Seizures. / Kawai, Hiromichi; Allende, Maria Laura; Wada, Ryuichi; Kono, Mari; Sango, Kazunori; Deng, Chuxia; Miyakawa, Tsuyoshi; Crawley, Jacqueline N.; Werth, Norbert; Bierfreund, Uwe; Sandhoff, Konrad; Proia, Richard L.

In: Journal of Biological Chemistry, Vol. 276, No. 10, 09.03.2001, p. 6885-6888.

Research output: Contribution to journalArticle

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T1 - Mice Expressing Only Monosialoganglioside GM3 Exhibit Lethal Audiogenic Seizures

AU - Kawai, Hiromichi

AU - Allende, Maria Laura

AU - Wada, Ryuichi

AU - Kono, Mari

AU - Sango, Kazunori

AU - Deng, Chuxia

AU - Miyakawa, Tsuyoshi

AU - Crawley, Jacqueline N.

AU - Werth, Norbert

AU - Bierfreund, Uwe

AU - Sandhoff, Konrad

AU - Proia, Richard L.

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N2 - 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.

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