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A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse

Jeans, Alexander F.; Oliver, Peter L.; Johnson, Reuben; Capogna, Marco; Vikman, Jenny; Molnar, Zoltan; Babbs, Arran; Partridge, Christopher J.; Salehi, Albert and Bengtsson, Martin LU , et al. (2007) In Proceedings of the National Academy of Sciences 104(7). p.2431-2436
Abstract
The neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic vesicle exocytosis, but its study has been limited by the neonatal lethality of murine SNARE knockouts. Here, we describe a viable mouse line carrying a mutation in the b-isoform of neuronal SNARE synaptosomal-associated protein of 25 kDa (SNAP-25) The causative I67T missense mutation results in increased binding affinities within the SNARE complex, impaired exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells, and a reduction in the amplitude of evoked cortical excitatory postsynaptic potentials. The mice also display ataxia and impaired sensorimotor gating, a phenotype which has been... (More)
The neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic vesicle exocytosis, but its study has been limited by the neonatal lethality of murine SNARE knockouts. Here, we describe a viable mouse line carrying a mutation in the b-isoform of neuronal SNARE synaptosomal-associated protein of 25 kDa (SNAP-25) The causative I67T missense mutation results in increased binding affinities within the SNARE complex, impaired exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells, and a reduction in the amplitude of evoked cortical excitatory postsynaptic potentials. The mice also display ataxia and impaired sensorimotor gating, a phenotype which has been associated with psychiatric disorders in humans. These studies therefore provide insights into the role of the SNARE complex in both diabetes and psychiatric disease. (Less)
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publication status
published
subject
keywords
attachment protein receptor, soluble N-ethylmaleimide-sensitive factor, diabetes, mutagenesis, exocytosis, schizophrenia
in
Proceedings of the National Academy of Sciences
volume
104
issue
7
pages
2431 - 2436
publisher
National Acad Sciences
external identifiers
  • wos:000244438500070
  • scopus:33847790078
ISSN
1091-6490
DOI
10.1073/pnas.0610222104
language
English
LU publication?
yes
id
2049b9b6-7832-4cba-ae7e-b23efaa715d5 (old id 672956)
alternative location
http://www.pnas.org/cgi/content/full/104/7/2431
date added to LUP
2007-12-12 13:00:45
date last changed
2017-11-05 03:35:18
@article{2049b9b6-7832-4cba-ae7e-b23efaa715d5,
  abstract     = {The neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic vesicle exocytosis, but its study has been limited by the neonatal lethality of murine SNARE knockouts. Here, we describe a viable mouse line carrying a mutation in the b-isoform of neuronal SNARE synaptosomal-associated protein of 25 kDa (SNAP-25) The causative I67T missense mutation results in increased binding affinities within the SNARE complex, impaired exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells, and a reduction in the amplitude of evoked cortical excitatory postsynaptic potentials. The mice also display ataxia and impaired sensorimotor gating, a phenotype which has been associated with psychiatric disorders in humans. These studies therefore provide insights into the role of the SNARE complex in both diabetes and psychiatric disease.},
  author       = {Jeans, Alexander F. and Oliver, Peter L. and Johnson, Reuben and Capogna, Marco and Vikman, Jenny and Molnar, Zoltan and Babbs, Arran and Partridge, Christopher J. and Salehi, Albert and Bengtsson, Martin and Eliasson, Lena and Rorsman, Patrik and Davies, Kay E.},
  issn         = {1091-6490},
  keyword      = {attachment protein receptor,soluble N-ethylmaleimide-sensitive factor,diabetes,mutagenesis,exocytosis,schizophrenia},
  language     = {eng},
  number       = {7},
  pages        = {2431--2436},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse},
  url          = {http://dx.doi.org/10.1073/pnas.0610222104},
  volume       = {104},
  year         = {2007},
}