Proceedings of the National Academy of Sciences - PNAS, 2007-02, Vol.104 (7), p.2431-2436
2007
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2007-02, Vol.104 (7), p.2431-2436
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 β-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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424, 1091-6490eISSN: 1091-6490DOI: 10.1073/pnas.0610222104Titel-ID: cdi_pnas_primary_104_7_2431_fulltext
- Format
- –
- Schlagworte
- Alcoholic Intoxication, Animals, Ataxia - genetics, attachment protein receptor, Behavioral neuroscience, Biological Sciences, Capacitance, Clinical Medicine, Diabetes, Diabetes Mellitus - etiology, Endocrinology and Diabetes, Endokrinologi och diabetes, Exocytosis, Exocytosis - genetics, Gait Disorders, Neurologic - genetics, Genes, Dominant, Genetic mutation, Insulin-Secreting Cells, Klinisk medicin, Medical and Health Sciences, Medicin och hälsovetenskap, Mental Disorders - etiology, Mice, Mice, Mutant Strains, Models, Animal, mutagenesis, Mutation, Missense, Neurons, Phenotypes, Recycling, Schizophrenia, SNARE proteins, SNARE Proteins - physiology, soluble N-ethylmaleimide-sensitive factor, Synaptic Vesicles - genetics, Synaptosomal-Associated Protein 25 - genetics, Synaptosomal-Associated Protein 25 - physiology