Proteomic Characterization of a Mouse Model of Familial Danish Dementia

Overview

Journal J Biomed Biotechnol

Specialty Biology

Date 2012 May 24

PMID 22619496

Citations 6

Authors

Monica Vitale

Giovanni Renzone

Shuji Matsuda

Andrea Scaloni

Luciano DAdamio

Nicola Zambrano

Affiliations

Soon will be listed here.

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 FDD(KI) 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 FDD(KI) 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 FDD(KI) mice.

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