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Updated: May 21, 2026
Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease
Published on: June 17, 2013
LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination
Kelly M Hinkle1, Mei Yue, Bahareh Behrouz
1Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Abstract:
Mutations in the LRRK2 gene are the most common cause of genetic Parkinson's disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation.We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis.Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes.
Insights
Loss of LRRK2 function in mice did not impair dopamine systems but caused behavioral changes and kidney degeneration. This study investigates LRRK2
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are a leading cause of genetic Parkinson's disease.
- The precise pathogenic mechanisms of LRRK2 mutations remain unclear, but suggested roles include neuronal polarity, neurotransmission, and protein degradation.
Purpose of the Study:
- To investigate the in vivo function of LRRK2 by creating and analyzing mice lacking exon 41, which encodes the kinase domain's activation hinge.
- To comprehensively assess the impact of LRRK2 loss on the dopaminergic system, behavior, and organ health up to 20 months of age.
Main Methods:
- Generation of LRRK2 knockout mice lacking exon 41.
- Evaluation of dopamine storage, release, uptake, and synthesis.
- Behavioral testing including open-field and rotarod tests.
- Analysis of dendritic spines, neurogenesis, and kidney pathology.
Main Results:
- The dopaminergic system in LRRK2 knockout mice showed no functional impairment.
- LRRK2 knockout mice exhibited altered exploratory activity and improved performance on the accelerated rotarod test.
- Loss of LRRK2 led to kidney degeneration with enhanced autophagic activity and autofluorescent material accumulation.
Conclusions:
- Loss of LRRK2 does not compromise the dopaminergic system but affects motor behavior and causes kidney pathology.
- The study highlights a role for LRRK2 in kidney homeostasis and suggests potential therapeutic targets for Parkinson's disease and related disorders.
