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Molecular Neurodegeneration

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Open Access 01-12-2012 | Research article

The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities

Authors: Tatsunori Maekawa, Sayuri Mori, Yui Sasaki, Takashi Miyajima, Sadahiro Azuma, Etsuro Ohta, Fumiya Obata

Published in: Molecular Neurodegeneration | Issue 1/2012

Abstract

Background

Leucine-rich repeat kinase 2 (LRRK2) is the gene responsible for autosomal-dominant Parkinson’s disease (PD), PARK8, but the mechanism by which LRRK2 mutations cause neuronal dysfunction remains unknown. In the present study, we investigated for the first time a transgenic (TG) mouse strain expressing human LRRK2 with an I2020T mutation in the kinase domain, which had been detected in the patients of the original PARK8 family.

Results

The TG mouse expressed I2020T LRRK2 in dopaminergic (DA) neurons of the substantia nigra, ventral tegmental area, and olfactory bulb. In both the beam test and rotarod test, the TG mice exhibited impaired locomotive ability in comparison with their non-transgenic (NTG) littermates. Although there was no obvious loss of DA neurons in either the substantia nigra or striatum, the TG brain showed several neurological abnormalities such as a reduced striatal dopamine content, fragmentation of the Golgi apparatus in DA neurons, and an increased degree of microtubule polymerization. Furthermore, the tyrosine hydroxylase-positive primary neurons derived from the TG mouse showed an increased frequency of apoptosis and had neurites with fewer branches and decreased outgrowth in comparison with those derived from the NTG controls.

Conclusions

The I2020T LRRK2 TG mouse exhibited impaired locomotive ability accompanied by several dopaminergic neuron abnormalities. The TG mouse should provide valuable clues to the etiology of PD caused by the LRRK2 mutation.

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Title: The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities
Authors: Tatsunori Maekawa
Sayuri Mori
Yui Sasaki
Takashi Miyajima
Sadahiro Azuma
Etsuro Ohta
Fumiya Obata
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2012
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-7-15

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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