DOI: 10.1523/jneurosci.4357-09.2009. Unexpected Lack of Hypersensitivity in LRRK2 Knock-Out Mice to MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine)

Unexpected Lack of Hypersensitivity in LRRK2 Knock-Out Mice to MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine)

10.1523/jneurosci.4357-09.2009

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Mutations in theleucine-rich repeat kinase 2(LRRK2) gene are the most common known cause of Parkinson's disease (PD). Whether loss of LRRK2 function accounts for neurodegeneration of dopamine neurons in PD is not known, nor is it known whether LRRK2 kinase activity modulates the susceptibility of dopamine (DA) neurons to the selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To better understand the role of LRRK2 in DA neuronal survival and its role in the susceptibility of DA neurons to MPTP, we generated LRRK2 knock-out (KO) mice lacking the kinase domain of LRRK2. Here, we show that LRRK2 KO mice are viable and have no major abnormalities and live to adulthood. The dopaminergic system is normal in LRRK2 KO mice as assessed via HPLC for DA and its metabolites and via stereologic assessment of DA neuron number in young and aged mice. Importantly, there is no significant difference in the susceptibility of LRRK2 KO and wild-type mice to MPTP. These results suggest that LRRK2 plays little if any role in the development and survival of DA neurons under physiologic conditions. Thus, PD due to LRRK2 mutations are likely not due to a loss of function. Moreover, LRRK2 is not required for the susceptibility of DA neurons to MPTP.

Bibliography

Andres-Mateos, E., Mejias, R., Sasaki, M., Li, X., Lin, B. M., Biskup, S., Zhang, L., Banerjee, R., Thomas, B., Yang, L., Liu, G., Beal, M. F., Huso, D. L., Dawson, T. M., & Dawson, V. L. (2009). Unexpected Lack of Hypersensitivity in LRRK2 Knock-Out Mice to MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine). The Journal of Neuroscience, 29(50), 15846â15850.

Authors 15

Eva Andres-Mateos (first)
Rebeca Mejias (additional)
Masayuki Sasaki (additional)
Xiaojie Li (additional)
Brian M. Lin (additional)
Saskia Biskup (additional)
Li Zhang (additional)
Rebecca Banerjee (additional)
Bobby Thomas (additional)
Lichuan Yang (additional)
Guosheng Liu (additional)
M. Flint Beal (additional)
David L. Huso (additional)
Ted M. Dawson (additional)
Valina L. Dawson (additional)

References 20 Referenced 101

Dates

Type	When
Created	15 years, 8 months ago (Dec. 16, 2009, 1:23 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 3:41 p.m.)
Indexed	1 week ago (Aug. 29, 2025, 5:51 a.m.)
Issued	15 years, 8 months ago (Dec. 16, 2009)
Published	15 years, 8 months ago (Dec. 16, 2009)
Published Online	15 years, 8 months ago (Dec. 16, 2009)
Published Print	15 years, 8 months ago (Dec. 16, 2009)

Funders 0

None

BibTeX

@article{Andres_Mateos_2009, title={Unexpected Lack of Hypersensitivity in LRRK2 Knock-Out Mice to MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine)}, volume={29}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.4357-09.2009}, DOI={10.1523/jneurosci.4357-09.2009}, number={50}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Andres-Mateos, Eva and Mejias, Rebeca and Sasaki, Masayuki and Li, Xiaojie and Lin, Brian M. and Biskup, Saskia and Zhang, Li and Banerjee, Rebecca and Thomas, Bobby and Yang, Lichuan and Liu, Guosheng and Beal, M. Flint and Huso, David L. and Dawson, Ted M. and Dawson, Valina L.}, year={2009}, month=dec, pages={15846–15850} }

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