Mice with Disrupted GM2/GD2 Synthase Gene Lack Complex Gangliosides but Exhibit Only Subtle Defects in their Nervous System

Gangliosides, sialic acid-containing glyco-sphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to play essential roles in establishment of the nervous system, especially in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (20), p.10662-10667
Main Authors: Takamiya, Kogo, Yamamoto, Akihito, Furukawa, Keiko, Yamashiro, Shuji, Shin, Masashi, Okada, Masahiko, Fukumoto, Satoshi, Haraguchi, Masashi, Takeda, Naoki, Fujimura, Koichi, Sakae, Mihoko, Kishikawa, Masao, Shiku, Hiroshi, Furukawa, Koichi, Aizawa, Shinichi
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal - physiology
Brain
Brain - anatomy & histology
Evoked potentials
Evoked Potentials, Somatosensory
Exons
G(M2) Ganglioside - physiology
Gangliosides
Gangliosides - physiology
Genes
Homozygotes
Liver
Magnification
Mice
Mice, Knockout
N-Acetylgalactosaminyltransferases - physiology
Nervous system
Nervous System Physiological Phenomena
Neural Conduction
Polypeptide N-acetylgalactosaminyltransferase
Somatosensory Cortex - physiology
Synapses
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Summary:Gangliosides, sialic acid-containing glyco-sphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to play essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted $\beta $1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.20.10662