ArticleMolecular neurodegeneration2012
The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Exploring LRRK2-dependent Mechanisms in Parkinson's Disease Therapy.CNS & neurological disorders drug targets · 2025Review
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.PLoS genetics · 2021Article
- LRRK2 inhibition potentiates PARP inhibitor cytotoxicity through inhibiting homologous recombination-mediated DNA double strand break repair.Clinical and translational medicine · 2021Article
- Review
- Pathogenic LRRK2 requires secondary factors to induce cellular toxicity.Bioscience reports · 2020Article
- Human Spinal Motor Neurons Are Particularly Vulnerable to Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients.International journal of molecular sciences · 2020Article
- From Synaptic Dysfunction to Neuroprotective Strategies in Genetic Parkinson's Disease: Lessons From LRRK2.Frontiers in cellular neuroscience · 2020Review
- Progress inFrontiers in neuroscience · 2020Review
- Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway.International journal of oncology · 2019Article
- Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo.Brain : a journal of neurology · 2018Article
- LRRK2 BAC transgenic rats develop progressive, L-DOPA-responsive motor impairment, and deficits in dopamine circuit function.Human molecular genetics · 2016Article
- The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research.The Biochemical journal · 2016Review
- Neural stem cells in Parkinson's disease: a role for neurogenesis defects in onset and progression.Cellular and molecular life sciences : CMLS · 2015Review
- LRRK2 pathobiology in Parkinson's disease.Journal of neurochemistry · 2014Review
- Conditional expression of Parkinson's disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration.Neurobiology of disease · 2014Article
- LRRK2, a puzzling protein: insights into Parkinson's disease pathogenesis.Experimental neurology · 2014Review
- Heterogeneity of leucine-rich repeat kinase 2 mutations: genetics, mechanisms and therapeutic implications.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
- Parkinson's disease: animal models and dopaminergic cell vulnerability.Frontiers in neuroanatomy · 2014Review
- The neurobiology of LRRK2 and its role in the pathogenesis of Parkinson's disease.Neurochemical research · 2014Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeucine-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.
resultsThe 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.
conclusionsThe 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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