| Summary: | <p>Abstract</p> <p>Mutations in the <it>LRRK2</it> gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of <it>LRRK2</it> mutations are still not clear, data emerging from <it>in vitro</it> and <it>in vivo</it> models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation.</p> <p>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.</p> <p>Our results show that the dopaminergic system was not functionally comprised in <it>LRRK2</it> knockout mice. However, <it>LRRK2</it> knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, <it>LRRK2</it> 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.</p>
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