Mutation of Tyrosine Sites in the Human Alpha-Synuclein Gene Induces Neurotoxicity in Transgenic Mice with Soluble Alpha-Synuclein Oligomer Formation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Generation of Transgenic Mouse Lines
2.2. Behavioral Tests
2.2.1. Open Field
2.2.2. Rotarod
2.2.3. Elevated Maze
2.2.4. Object Exploration Test
2.2.5. Force Test
2.2.6. Hind-Limb Clasping Test
2.2.7. Adhesive Removal Test
2.2.8. Gait Analysis
2.3. mRNA Extraction and qPCR
2.4. Western Blotting
2.5. Immunohistochemistry
2.6. Quantification of Aggregate Size
2.7. Oligomer/Total α-Synuclein ELISA
2.8. Microtubule Retraction Assay
2.9. Statistics
3. Results
3.1. YF Mice Express α-Synuclein at Lower Levels Than ASO Mice
3.2. YF Mice Are Severely Motor-Impaired
3.3. YF Mice Accumulate α-Synuclein in the Synaptosomes
3.4. YF Mice Have High Amounts of Soluble α-Synuclein Oligomers
3.5. YF Have High Amounts of α-Synuclein in Cerebral Cortex and Limbic Structures
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Lassen, L.B.; Thomsen, M.S.; Basso, E.; Füchtbauer, E.-M.; Füchtbauer, A.; Outeiro, T.F.; Jensen, P.H.; Moos, T. Mutation of Tyrosine Sites in the Human Alpha-Synuclein Gene Induces Neurotoxicity in Transgenic Mice with Soluble Alpha-Synuclein Oligomer Formation. Cells 2022, 11, 3673. https://doi.org/10.3390/cells11223673
Lassen LB, Thomsen MS, Basso E, Füchtbauer E-M, Füchtbauer A, Outeiro TF, Jensen PH, Moos T. Mutation of Tyrosine Sites in the Human Alpha-Synuclein Gene Induces Neurotoxicity in Transgenic Mice with Soluble Alpha-Synuclein Oligomer Formation. Cells. 2022; 11(22):3673. https://doi.org/10.3390/cells11223673
Chicago/Turabian StyleLassen, Louise Berkhoudt, Maj Schneider Thomsen, Elisa Basso, Ernst-Martin Füchtbauer, Annette Füchtbauer, Tiago Fleming Outeiro, Poul Henning Jensen, and Torben Moos. 2022. "Mutation of Tyrosine Sites in the Human Alpha-Synuclein Gene Induces Neurotoxicity in Transgenic Mice with Soluble Alpha-Synuclein Oligomer Formation" Cells 11, no. 22: 3673. https://doi.org/10.3390/cells11223673