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Research ArticleResearch Article: Negative Results, Disorders of the Nervous System

Alpha-Synuclein Phosphomimetic Y39E and S129D Knock-In Mice Show Cytosolic Alpha-Synuclein Localization without Developing Neurodegeneration or Motor Deficits

YoungDoo Kim, Bhupesh Vaidya, Joseph McInnes and Huda Y. Zoghbi
eNeuro 31 March 2025, 12 (4) ENEURO.0357-24.2025; https://doi.org/10.1523/ENEURO.0357-24.2025
YoungDoo Kim
1Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030
2Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas 77030
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Bhupesh Vaidya
1Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030
2Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas 77030
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Joseph McInnes
1Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030
2Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas 77030
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Huda Y. Zoghbi
1Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030
2Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas 77030
3Department of Neuroscience, BCM, Houston, Texas 77030
4Department of Pediatrics, BCM, Houston, Texas 77030
5Department of Neurology, BCM, Houston, Texas 77030
6Howard Hughes Medical Institute, Houston, Texas 77030
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Article Information

DOI 
https://doi.org/10.1523/ENEURO.0357-24.2025
PubMed 
40164505
Published By 
Society for Neuroscience
History 
  • Received August 15, 2024
  • Revision received February 9, 2025
  • Accepted February 12, 2025
  • Published online March 31, 2025.
Copyright & Usage 
Copyright © 2025 Kim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Author Information

  1. YoungDoo Kim1,2,
  2. Bhupesh Vaidya1,2,
  3. Joseph McInnes1,2 and
  4. Huda Y. Zoghbi1,2,3,4,5,6
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030
  2. 2Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas 77030
  3. 3Department of Neuroscience, BCM, Houston, Texas 77030
  4. 4Department of Pediatrics, BCM, Houston, Texas 77030
  5. 5Department of Neurology, BCM, Houston, Texas 77030
  6. 6Howard Hughes Medical Institute, Houston, Texas 77030
  1. Correspondence should be addressed to Huda Y. Zoghbi at hzoghbi{at}bcm.edu.
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Author contributions

  1. Author contributions: Y.K., J.M., and H.Y.Z. designed research; Y.K., B.V., and J.M. performed research; Y.K. contributed unpublished reagents/analytic tools; Y.K. and H.Y.Z. analyzed data; Y.K. and H.Y.Z. wrote the paper.

Disclosures

  • H.Y.Z. cofounded Cajal Neuroscience, is a Director of Regeneron Pharmaceuticals board, and is on the scientific advisory board of Cajal Neuroscience, Lyterian, and the Column Group.

  • We appreciate Kristyn Gonzales, Yanhong Wei Liang, and Surabi Veeraragavan's technical support. We thank Jiyoen Kim, Xue Deng, and Hamin Lee for their critical comments on the manuscript. We further thank the Baylor College of Medicine (BCM), Genetically Engineered Mouse Core, and the following cores (Microscopy Core and Animal Behavior Core) supported by the Jan and Dan Duncan Neurological Research Institute (NRI) and the BCM-IDDRC (U54HD083092) from the Eunice Kennedy Shriver National Institute of Child Health and Development. This work is supported by the Huffington Foundation and Howard Hughes Medical Institute.

Funding

  • Huffington Foundation

  • Howard Hughes Medical Institute (HHMI)

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Alpha-Synuclein Phosphomimetic Y39E and S129D Knock-In Mice Show Cytosolic Alpha-Synuclein Localization without Developing Neurodegeneration or Motor Deficits
YoungDoo Kim, Bhupesh Vaidya, Joseph McInnes, Huda Y. Zoghbi
eNeuro 31 March 2025, 12 (4) ENEURO.0357-24.2025; DOI: 10.1523/ENEURO.0357-24.2025

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Alpha-Synuclein Phosphomimetic Y39E and S129D Knock-In Mice Show Cytosolic Alpha-Synuclein Localization without Developing Neurodegeneration or Motor Deficits
YoungDoo Kim, Bhupesh Vaidya, Joseph McInnes, Huda Y. Zoghbi
eNeuro 31 March 2025, 12 (4) ENEURO.0357-24.2025; DOI: 10.1523/ENEURO.0357-24.2025
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Keywords

  • alpha-synuclein
  • phosphomimetic mutants
  • S129D
  • Y39E

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