PMID- 10611374
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 26
DP  - 1999 Dec 21
TI  - Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A).
PG  - 15268-73
AB  - 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 homolog 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 gamma-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.
FAU - Crowder, K M
AU  - Crowder KM
AD  - Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
FAU - Gunther, J M
AU  - Gunther JM
FAU - Jones, T A
AU  - Jones TA
FAU - Hale, B D
AU  - Hale BD
FAU - Zhang, H Z
AU  - Zhang HZ
FAU - Peterson, M R
AU  - Peterson MR
FAU - Scheller, R H
AU  - Scheller RH
FAU - Chavkin, C
AU  - Chavkin C
FAU - Bajjalieh, S M
AU  - Bajjalieh SM
LA  - eng
GR  - T32 DA007278/DA/NIDA NIH HHS/United States
GR  - R01 MH059842/MH/NIMH NIH HHS/United States
GR  - NS33898/NS/NINDS NIH HHS/United States
GR  - R01 MH59842-01/MH/NIMH NIH HHS/United States
GR  - DA07278/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Sv2a protein, mouse)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - Brain/anatomy & histology
MH  - Endocrine System/abnormalities
MH  - Genes, Lethal
MH  - Hippocampus/*physiology
MH  - Homozygote
MH  - Membrane Glycoproteins/*deficiency/genetics
MH  - Mice
MH  - Mice, Knockout/growth & development
MH  - Mutagenesis
MH  - Nerve Tissue Proteins/*deficiency/genetics
MH  - Nervous System Malformations
MH  - Protein Isoforms
MH  - Seizures/genetics
MH  - Synapses/ultrastructure
MH  - Synaptic Transmission/*physiology
MH  - gamma-Aminobutyric Acid/metabolism
PMC - PMC24809
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - 10.1073/pnas.96.26.15268 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15268-73. doi:
      10.1073/pnas.96.26.15268.