Effects of Mouse Alpha-Synuclein Overexpression in Mice
Author Information
Author(s): Rieker Claus, Dev Kumlesh K., Lehnhoff Katja, Barbieri Samuel, Ksiazek Iwona, Kauffmann Sabine, Danner Simone, Schell Heinrich, Boden Cindy, Ruegg Markus A., Kahle Philipp J., van der Putten Herman, Shimshek Derya R.
Primary Institution: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
Hypothesis
Does overexpression of wildtype mouse alpha-synuclein lead to neurodegenerative changes similar to those seen in human diseases?
Conclusion
Increased levels of wildtype mouse alpha-synuclein do not cause early-onset behavior changes but lead to end-stage pathophysiological changes in neurons.
Supporting Evidence
- Transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem.
- Neuronal Ser129-phosphorylated alpha-synuclein occurred in aggregates in affected brain regions.
- Thy1-mouse alpha-synuclein mice displayed increased mortality compared to wildtype littermates.
- Motor performance declined significantly after 6 months of age in transgenic mice.
Takeaway
Mice with extra mouse alpha-synuclein didn't show problems until they got older, but when they did, it was similar to what happens in humans with certain brain diseases.
Methodology
Transgenic mice were created to express mouse alpha-synuclein, and various behavioral and pathological analyses were conducted.
Potential Biases
Potential bias due to funding from Novartis Pharma AG, which may influence study outcomes.
Limitations
The study was limited by the short lifespan of the transgenic mice, which may not allow for the observation of long-term effects.
Participant Demographics
Transgenic C57BL/6 mice were used in the study.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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