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Although the mechanisms behind the pathogenic effects of<jats:italic>LRRK2<\/jats:italic>mutations are still not clear, data emerging from<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation.<\/jats:p><jats: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.<\/jats:p><jats:p>Our results show that the dopaminergic system was not functionally comprised in<jats:italic>LRRK2<\/jats:italic>knockout mice. However,<jats:italic>LRRK2<\/jats:italic>knockout mice displayed abnormal exploratory activity in the open-field test. Moreover,<jats:italic>LRRK2<\/jats:italic>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.<\/jats:p>","DOI":"10.1186\/1750-1326-7-25","type":"journal-article","created":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T21:21:02Z","timestamp":1347484862000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":161,"title":["LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors"],"prefix":"10.1186","volume":"7","author":[{"given":"Kelly M","family":"Hinkle","sequence":"first","affiliation":[]},{"given":"Mei","family":"Yue","sequence":"additional","affiliation":[]},{"given":"Bahareh","family":"Behrouz","sequence":"additional","affiliation":[]},{"given":"Justus C","family":"D\u00e4chsel","sequence":"additional","affiliation":[]},{"given":"Sarah J","family":"Lincoln","sequence":"additional","affiliation":[]},{"given":"Erin E","family":"Bowles","sequence":"additional","affiliation":[]},{"given":"Joel E","family":"Beevers","sequence":"additional","affiliation":[]},{"given":"Brittany","family":"Dugger","sequence":"additional","affiliation":[]},{"given":"Beate","family":"Winner","sequence":"additional","affiliation":[]},{"given":"Iryna","family":"Prots","sequence":"additional","affiliation":[]},{"given":"Caroline B","family":"Kent","sequence":"additional","affiliation":[]},{"given":"Kenya","family":"Nishioka","sequence":"additional","affiliation":[]},{"given":"Wen-Lang","family":"Lin","sequence":"additional","affiliation":[]},{"given":"Dennis W","family":"Dickson","sequence":"additional","affiliation":[]},{"given":"Christopher J","family":"Janus","sequence":"additional","affiliation":[]},{"given":"Matthew J","family":"Farrer","sequence":"additional","affiliation":[]},{"given":"Heather L","family":"Melrose","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,5,30]]},"reference":[{"key":"343_CR1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","volume":"44","author":"A Zimprich","year":"2004","unstructured":"Zimprich A, et al: Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. 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