title: Proteomic characterization of a mouse model of familial Danish dementia.
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.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Vitale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Renzone
authors.forename: Shuji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Luciano
authors.initials: L
authors.lastname: D'Adamio
authors.forename: Nicola
authors.initials: N
authors.lastname: Zambrano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002386:Cataract / Q000378:metabolism*; D002524:Cerebellar Ataxia / Q000378:metabolism*; D003638:Deafness / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D020543:Proteome