<it>LRRK2</it> knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors

• Main Authors: Hinkle Kelly M, Yue Mei, Behrouz Bahareh, Dächsel Justus C, Lincoln Sarah J, Bowles Erin E, Beevers Joel E, Dugger Brittany, Winner Beate, Prots Iryna, Kent Caroline B, Nishioka Kenya, Lin Wen-Lang, Dickson Dennis W, Janus Christopher J, Farrer Matthew J, Melrose Heather L
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: Molecular Neurodegeneration
• Subjects: Parkinson’s disease; Knockout; Dopamine; Microdialysis; Neuropathology; Open-field; Motor co-ordination; Kidney; Autophagy
• Online Access: http://www.molecularneurodegeneration.com/content/7/1/25

<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>