Marco Capogna

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Alexander F Jeans, Medical Research Council Functional Genetics Unit, University of Oxford, South Parks Road, Oxford, OX1 3QX, United Kingdom.
  • ,
  • Peter L Oliver
  • ,
  • Reuben Johnson
  • ,
  • Marco Capogna
  • Jenny Vikman
  • ,
  • Zoltán Molnár
  • ,
  • Arran Babbs
  • ,
  • Christopher J Partridge
  • ,
  • Albert Salehi
  • ,
  • Martin Bengtsson
  • ,
  • Lena Eliasson
  • ,
  • Patrik Rorsman
  • ,
  • Kay E Davies

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue7
Pages (from-to)2431-6
Number of pages6
ISSN0027-8424
DOIs
Publication statusPublished - 13 Feb 2007

    Research areas

  • Alcoholic Intoxication, Animals, Ataxia/genetics, Diabetes Mellitus/etiology, Exocytosis/genetics, Gait Disorders, Neurologic/genetics, Genes, Dominant, Insulin-Secreting Cells, Mental Disorders/etiology, Mice, Mice, Mutant Strains, Models, Animal, Mutation, Missense, SNARE Proteins/physiology, Synaptic Vesicles/genetics, Synaptosomal-Associated Protein 25/genetics

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