Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/73037
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency |
Other Titles: | Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3 zeta deficiency |
Author: | Cheah, P. Ramshaw, H. Thomas, P. Toyo-oka, K. Xu, X. Martin, S. Coyle, P. Guthridge, M. Stomski, F. van den Buuse, M. Wynshaw-Boris, A. Lopez, A. Schwarz, Q. |
Citation: | Molecular Psychiatry, 2012; 17(4):451-466 |
Publisher: | Nature Publishing Group |
Issue Date: | 2012 |
ISSN: | 1359-4184 1476-5578 |
Statement of Responsibility: | P-S Cheah, HS Ramshaw, PQ Thomas, K Toyo-oka, X Xu, S Martin, P Coyle, MA Guthridge, F Stomski, M van den Buuse, A Wynshaw-Boris, AF Lopez and QP Schwarz |
Abstract: | Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-Deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network. |
Keywords: | Neurodevelopment neuropsychiatric disorder schizophrenia synapse 14-3-3ζ |
Rights: | © 2012 Macmillan Publishers Limited |
DOI: | 10.1038/mp.2011.158 |
Published version: | http://dx.doi.org/10.1038/mp.2011.158 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.