Institut for Biomedicin

Marco Capogna

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

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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.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind104
Nummer7
Sider (fra-til)2431-6
Antal sider6
ISSN0027-8424
DOI
StatusUdgivet - 13 feb. 2007

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