Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. We created a LRRK2 transgenic mouse model that recapitulates cardinal features of the disease: an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection. These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: LRRK2R1441G BAC mice develop age-dependent motor deficits that responds to levodopa and apomorphine.
Figure 2: Neurochemical deficits in LRRK2R1441G mice.
Figure 3: Morphologic abnormalities of mesencephalic dopamine neurons and their axons in LRRK2R1441G BAC transgenic mice.

Similar content being viewed by others

References

  1. Zimprich, A. et al. Neuron 44, 601–607 (2004).

    Article  CAS  Google Scholar 

  2. Paisán-Ruíz, C. et al. Neuron 44, 595–600 (2004).

    Article  Google Scholar 

  3. Di Fonzo, A. et al. Lancet 365, 412–415 (2005).

    Article  CAS  Google Scholar 

  4. Gilks, W.P. et al. Lancet 365, 415–416 (2005).

    CAS  PubMed  Google Scholar 

  5. Saunders-Pullman, R. et al. Neurosci. Lett. 402, 92–96 (2006).

    Article  CAS  Google Scholar 

  6. Polymeropoulos, M.H. et al. Science 276, 2045–2047 (1997).

    Article  CAS  Google Scholar 

  7. Ballatore, C., Lee, V.M. & Trojanowski, J.Q. Nat. Rev. Neurosci. 8, 663–672 (2007).

    Article  CAS  Google Scholar 

  8. Tobin, J.E. et al. Neurology 71, 28–34 (2008).

    Article  CAS  Google Scholar 

  9. Dauer, W. & Przedborski, S. Neuron 39, 889–909 (2003).

    Article  CAS  Google Scholar 

  10. Melrose, H.L. et al. Neuroscience 147, 1047–1058 (2007).

    Article  CAS  Google Scholar 

  11. El-Khodor, B.F. & Burke, R.E. J. Comp. Neurol. 452, 65–79 (2002).

    Article  Google Scholar 

  12. Büki, A., Okonkwo, D.O., Wang, K.K. & Povlishock, J.T. J. Neurosci. 20, 2825–2834 (2000).

    Article  Google Scholar 

  13. Kerschensteiner, M., Schwab, M.E., Lichtman, J.W. & Misgeld, T. Nat. Med. 11, 572–577 (2005).

    Article  CAS  Google Scholar 

  14. Duda, J.E., Giasson, B.I., Mabon, M.E., Lee, V.M. & Trojanowski, J.Q. Ann. Neurol. 52, 205–210 (2002).

    Article  CAS  Google Scholar 

  15. Biernat, J. et al. EMBO J. 11, 1593–1597 (1992).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank K. Merchant and her team at Eli Lilly and Company for generating the immunoblot data that facilitated selection of transgenic lines, S. Fleming and M.-F. Chesselet for advice on behavioral studies, and X. William Yang and A. Yamamoto for insightful discussions. This work was supported in part by grants from the Michael J. Fox Foundation and the US National Institutes of Health to C.L., from the Department of Defense to M.F.B., and from US National Institutes of Health and the Parkinson's Disease Foundation to R.E.B. and T.F.O.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chenjian Li.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 and Supplementary Methods (PDF 7201 kb)

Supplementary Video 1

Home cage behavior of 10-month-old wild-type nontransgenic littermates that moved normally, and LRRK2R1441G BAC transgenic mice that became immobile (akinesia-like). The movie is real time. (AVI 1582 kb)

Supplementary Video 2

Open field tests of 10-month-old wild-type nontransgenic littermates that moved normally. (AVI 2446 kb)

Supplementary Video 3

Open field tests of 10-month-old LRRK2R1441G BAC transgenic mice that became immobile. (AVI 1563 kb)

Supplementary Video 4

Cylinder test of 10-month-old wild-type nontransgenic littermates that moved and reared normally. (AVI 1500 kb)

Supplementary Video 5

Cylinder test of 10-month-old LRRK2R1441G BAC transgenic mice that became immobile. (AVI 557 kb)

Supplementary Video 6

Rescue of the motor deficit in LRRK2R1441G BAC transgenic mice by levodopa. Home cage behavior of 10-month-old LRRK2R1441G BAC transgenic mice about 1.5 h post levodopa injection. There was a significant increase of motor activity. The movie is real time. (AVI 987 kb)

Supplementary Video 7

Rescue of the motor deficit in LRRK2R1441G BAC transgenic mice by levodopa. Open field test of 10-month-old LRRK2R1441G BAC transgenic mice about 40 min post levodopa injection. There was a significant increase of motor activity. The movie is real time. (AVI 2092 kb)

Supplementary Video 8

Rescue of the motor deficit in LRRK2R1441G BAC transgenic mice by levodopa. Cylinder test of 10-month-old LRRK2R1441G BAC transgenic mice about 1 h post levodopa injection. There was a significant increase of motor activity. The movie is real time. (AVI 2092 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Y., Liu, W., Oo, T. et al. Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci 12, 826–828 (2009). https://doi.org/10.1038/nn.2349

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.2349

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing