A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/672956
- author
- organization
- publishing date
- 2007
- type
- Contribution to journal
- 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 Academy of 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
- 2016-04-01 11:55:55
- date last changed
- 2022-02-18 07:25:02
@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}}, keywords = {{attachment protein receptor; soluble N-ethylmaleimide-sensitive factor; diabetes; mutagenesis; exocytosis; schizophrenia}}, language = {{eng}}, number = {{7}}, pages = {{2431--2436}}, publisher = {{National Academy of 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}}, doi = {{10.1073/pnas.0610222104}}, volume = {{104}}, year = {{2007}}, }