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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes

Nyckelord

Originalspråkengelska
Sidor (från-till)2431-2436
TidskriftProceedings of the National Academy of Sciences
Volym104
Utgivningsnummer7
StatusPublished - 2007
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Vikman, J., 2008, Department of Clinical Sciences, Lund University. 114 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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