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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 728178, 8 pages
http://dx.doi.org/10.1155/2012/728178
Research Article

Proteomic Characterization of a Mouse Model of Familial Danish Dementia

1Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy
2CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy
3Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Napoli, Italy
4Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10462, USA

Received 30 December 2011; Accepted 2 February 2012

Academic Editor: Monica Fedele

Copyright © 2012 Monica Vitale et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A dominant mutation in the ITM2B/BRI2 gene causes familial Danish dementia (FDD) in humans. To model FDD in animal systems, a knock-in approach was recently implemented in mice expressing a wild-type and mutant allele, which bears the FDD-associated mutation. Since these F D D K I mice show behavioural alterations and impaired synaptic function, we characterized their synaptosomal proteome via two-dimensional differential in-gel electrophoresis. After identification by nanoliquid chromatography coupled to electrospray-linear ion trap tandem mass spectrometry, the differentially expressed proteins were classified according to their gene ontology descriptions and their predicted functional interactions. The Dlg4/Psd95 scaffold protein and additional signalling proteins, including protein phosphatases, were revealed by STRING analysis as potential players in the altered synaptic function of F D D K I mice. Immunoblotting analysis finally demonstrated the actual downregulation of the synaptosomal scaffold protein Dlg4/Psd95 and of the dual-specificity phosphatase Dusp3 in the synaptosomes of F D D K I mice.