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

Research output: Contribution to journalArticle


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.


  • Alexander F. Jeans
  • Peter L. Oliver
  • Reuben Johnson
  • Marco Capogna
  • Jenny Vikman
  • Zoltan Molnar
  • Arran Babbs
  • Christopher J. Partridge
  • Albert Salehi
  • Martin Bengtsson
  • Lena Eliasson
  • Patrik Rorsman
  • Kay E. Davies
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • attachment protein receptor, soluble N-ethylmaleimide-sensitive factor, diabetes, mutagenesis, exocytosis, schizophrenia
Original languageEnglish
Pages (from-to)2431-2436
JournalProceedings of the National Academy of Sciences
Issue number7
Publication statusPublished - 2007
Publication categoryResearch

Related research output

Jenny Vikman, 2008, Department of Clinical Sciences, Lund University. 114 p.

Research output: ThesisDoctoral Thesis (compilation)

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