Reference : Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 lead...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice.
Nuber, Silke [> >]
Franck, Thomas [> >]
Wolburg, Hartwig [> >]
Schumann, Ulrike [> >]
Casadei, Nicolas [> >]
Fischer, Kristina [> >]
Calaminus, Carsten [> >]
Pichler, Bernd J. [> >]
Chanarat, Sittinan [> >]
Teismann, Peter [> >]
Schulz, Jorg B. [> >]
Luft, Andreas R. [> >]
Tomiuk, Jurgen [> >]
Wilbertz, Johannes [> >]
Bornemann, Antje [> >]
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Riess, Olaf [> >]
Yes (verified by ORBilu)
United States
[en] Animals ; Brain/pathology ; Carrier Proteins/genetics ; Female ; Humans ; Immunohistochemistry/methods ; Male ; Mice ; Mice, Transgenic ; Microscopy, Electron/methods ; Models, Genetic ; Nerve Tissue Proteins/genetics ; Neurotransmitter Agents/metabolism ; Positron-Emission Tomography/methods ; Purkinje Cells/metabolism ; Transgenes ; alpha-Synuclein/metabolism
[en] Synphilin-1 has been identified as an interacting protein of alpha-synuclein, Parkin, and LRRK2, proteins which are mutated in familial forms of Parkinson disease (PD). Subsequently, synphilin-1 has also been shown to be an intrinsic component of Lewy bodies in sporadic PD. In order to elucidate the role of synphilin-1 in the pathogenesis of PD, we generated transgenic mice overexpressing wild-type and mutant (R621C) synphilin-1 driven by a mouse prion protein promoter. Transgenic expression of both wild-type and the R621C variant synphilin-1 resulted in increased dopamine levels of the nigrostriatal system in 3-month-old mice. Furthermore, we found pathological ubiquitin-positive inclusions in cerebellar sections and dark-cell degeneration of Purkinje cells. Both transgenic mouse lines showed significant reduction of motor skill learning and motor performance. These findings suggest a pathological role of overexpressed synphilin-1 in vivo and will help to further elucidate the mechanisms of protein aggregation and neuronal cell death.
Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)

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