Article (Scientific journals)
Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice.
Nuber, Silke; Franck, Thomas; Wolburg, Hartwig et al.
2010In Neurogenetics, 11 (1), p. 107-20
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Keywords :
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
Abstract :
[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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
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 ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Riess, Olaf
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Title :
Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice.
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Springer, Germany
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Peer reviewed :
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