Abnormal Neurotransmission in Mice Lacking Synaptic Vesicle Protein 2A (SV2A)

Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homology in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and p...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-12, Vol.96 (26), p.15268-15273
Main Authors: Crowder, Kelly M., Gunther, Jane M., Jones, Theresa A., Hale, Brian D., Zhang, Hai Zhuan, Peterson, Michael R., Scheller, Richard H., Chavkin, Charles, Bajjalieh, Sandra M.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Biology
Brain
Brain - anatomy & histology
Central nervous system
Endocrine System - abnormalities
gamma-Aminobutyric Acid - metabolism
Genes, Lethal
Hippocampus
Hippocampus - physiology
Homozygote
Membrane Glycoproteins - deficiency
Membrane Glycoproteins - genetics
Mice
Mice, Knockout - growth & development
Mutagenesis
Nerve Tissue Proteins - deficiency
Nerve Tissue Proteins - genetics
Nervous System Malformations
Neurology
Neurons
Neurotransmission
Phenotypes
Postsynaptic density
Protein Isoforms
Proteins
Rodents
Seizures
Seizures - genetics
Synapses
Synapses - ultrastructure
Synaptic Transmission - physiology
synaptic vesicle protein 2
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Summary:Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homology in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and protein interactions of SV2 suggest multiple possible functions, its role in synaptic events remains unknown. To explore the function of SV2 in an in vivo context, we generated mice that do not express the primary SV2 isoform, SV2A, by using targeted gene disruption. Animals homozygous for the SV2A gene disruption appear normal at birth. However, they fail to grow, experience severe seizures, and die within 3 weeks, suggesting multiple neural and endocrine deficits. Electrophysiological studies of spontaneous inhibitory neurotransmission in the CA3 region of the hippocampus revealed that loss of SV2A leads to a reduction in action potential-dependent γ -aminobutyric acid (GABA)ergic neurotransmission. In contrast, action potential-independent neurotransmission was normal. Analyses of synapse ultrastructure suggest that altered neurotransmission is not caused by changes in synapse density or morphology. These findings demonstrate that SV2A is an essential protein and implicate it in the control of exocytosis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.26.15268