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Research ArticleNew Research, Disorders of the Nervous System

Overexpression of Parkinson’s Disease-Associated Mutation LRRK2 G2019S in Mouse Forebrain Induces Behavioral Deficits and α-Synuclein Pathology

Yulan Xiong, Stewart Neifert, Senthilkumar S. Karuppagounder, Jeannette N. Stankowski, Byoung Dae Lee, Jonathan C. Grima, Guanxing Chen, Han Seok Ko, Yunjong Lee, Debbie Swing, Lino Tessarollo, Ted M. Dawson and Valina L. Dawson
eNeuro 6 March 2017, 4 (2) ENEURO.0004-17.2017; DOI: https://doi.org/10.1523/ENEURO.0004-17.2017
Yulan Xiong
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
8Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, Kansas 66506
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  • ORCID record for Yulan Xiong
Stewart Neifert
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Senthilkumar S. Karuppagounder
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Jeannette N. Stankowski
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Byoung Dae Lee
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Jonathan C. Grima
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
3Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Guanxing Chen
8Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, Kansas 66506
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Han Seok Ko
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Yunjong Lee
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Debbie Swing
9Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702
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Lino Tessarollo
9Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702
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Ted M. Dawson
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
3Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
5Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
6Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130
7Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130
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Valina L. Dawson
1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
3Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
6Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130
7Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130
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Article Information

DOI 
https://doi.org/10.1523/ENEURO.0004-17.2017
PubMed 
28321439
Published By 
Society for Neuroscience
History 
  • Received January 4, 2017
  • Revision received February 27, 2017
  • Accepted March 1, 2017
  • Published online March 6, 2017.
Copyright & Usage 
Copyright © 2017 Xiong 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. Yulan Xiong1,2,8,
  2. Stewart Neifert1,2,
  3. Senthilkumar S. Karuppagounder1,2,
  4. Jeannette N. Stankowski1,2,
  5. Byoung Dae Lee1,2,
  6. Jonathan C. Grima1,2,3,
  7. Guanxing Chen8,
  8. Han Seok Ko1,2,
  9. Yunjong Lee1,2,
  10. Debbie Swing9,
  11. Lino Tessarollo9,
  12. Ted M. Dawson1,2,3,5,6,7 and
  13. Valina L. Dawson1,2,3,4,6,7
  1. 1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  2. 2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  3. 3Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  4. 4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  5. 5Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  6. 6Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130
  7. 7Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130
  8. 8Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, Kansas 66506
  9. 9Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702
  1. Correspondence should be addressed to either of the following: Valina L. Dawson, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway, MRB 731, Baltimore, MD 21205, E-mail: vdawson{at}jhmi.edu; or Yulan Xiong, Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, 212 Coles Hall, Manhattan, KS 66506, E-mail: yulanxiong{at}ksu.edu.
  • J.N. Stankowski’s present address: Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224.

  • B.D. Lee’s present address: Age-Related and Brain Disease Research Center, Department of Neuroscience, Kyung Hee University, Seoul 130-701, South Korea.

  • Y. Lee’s present address: Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 446-746, South Korea.

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Author contributions

  1. Author Contributions: Y.X., H.S.K., T.M.D. and V.L.D. designed research; Y.X., S.N., S.S.K., J.N.S., B.D.L., J.C.G., G.C., Y.L., D.S., and L.T. performed research; Y.X., S.N., S.S.K., J.N.S., B.D.L., J.C.G., G.C., Y.L., D.S., and L.T. analyzed data; Y.X., S.N., T.M.D., and V.L.D. wrote the paper.

  • J.N. Stankowski’s present address: Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224.

  • B.D. Lee’s present address: Age-Related and Brain Disease Research Center, Department of Neuroscience, Kyung Hee University, Seoul 130-701, South Korea.

  • Y. Lee’s present address: Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 446-746, South Korea.

Disclosures

  • The authors report no competing financial interests.

  • This work was supported from National Institutes of Health (NIH)/National Institute on Aging Grant K01-AG046366 (Y.X.), the William N. & Bernice E. Bumpus Foundation Innovation Awards (Y.X.), start-up fund and SUCCESS-FYI Intramural Grant from Kansas State University College of Veterinary Medicine (Y.X.), National Science Foundation Graduate Research Fellowship Award (J.C.G.), the Thomas Shortman Training Fund Graduate Scholarship Award (J.C.G.), the Axol Science Scholarship Award (J.C.G.), NIH/National Institute of Neurological Disorders and Stroke (NINDS) Grant NS-082205 (H.S.K.), NIH/NINDS Grant NS-38377 (H.S.K., T.M.D., and V.L.D.), and the JPB Foundation (T.M.D.). T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. The authors acknowledge the joint participation by the Adrienne Helis Malvin Medical Research Foundation and the Diana Helis Henry Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with The Johns Hopkins Hospital, the Johns Hopkins University School of Medicine, and the Foundation's Parkinson's Disease Programs.

Funding

  • HHS | NIH | National Institute on Aging (NIA)

    100000049; AG046366
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)

    100000065; NS082205
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)

    100000065; NS38377

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  • You are viewing the most recent version of this article.
  • previous version (March 06, 2017).

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Mar 201709145
Apr 201755122134
May 2017348097
Jun 2017195879
Jul 2017145671
Aug 20175811390
Sep 20175212286
Oct 20175012579
Nov 201765124121
Dec 20174328928
Total 20173901180830
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Apr 20183811897
May 20181610324
Jun 2018219852
Jul 2018213131
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Mar 20191514418
Apr 201998425
May 201965633
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Total 2019118848193
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Feb 202063816
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May 202013821
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Jul 202025310
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Total 202064546136
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Apr 20214634
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Jun 202127116
Jul 20212759
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Total 202140890151
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Apr 20220406
May 202276610
Jun 202218214
Jul 202224711
Aug 20221359
Sep 202235012
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Total 202232609132
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Total 2023214235
Total93058951895
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Overexpression of Parkinson’s Disease-Associated Mutation LRRK2 G2019S in Mouse Forebrain Induces Behavioral Deficits and α-Synuclein Pathology
Yulan Xiong, Stewart Neifert, Senthilkumar S. Karuppagounder, Jeannette N. Stankowski, Byoung Dae Lee, Jonathan C. Grima, Guanxing Chen, Han Seok Ko, Yunjong Lee, Debbie Swing, Lino Tessarollo, Ted M. Dawson, Valina L. Dawson
eNeuro 6 March 2017, 4 (2) ENEURO.0004-17.2017; DOI: 10.1523/ENEURO.0004-17.2017

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Overexpression of Parkinson’s Disease-Associated Mutation LRRK2 G2019S in Mouse Forebrain Induces Behavioral Deficits and α-Synuclein Pathology
Yulan Xiong, Stewart Neifert, Senthilkumar S. Karuppagounder, Jeannette N. Stankowski, Byoung Dae Lee, Jonathan C. Grima, Guanxing Chen, Han Seok Ko, Yunjong Lee, Debbie Swing, Lino Tessarollo, Ted M. Dawson, Valina L. Dawson
eNeuro 6 March 2017, 4 (2) ENEURO.0004-17.2017; DOI: 10.1523/ENEURO.0004-17.2017
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Keywords

  • Parkinson’s disease
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