LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors
| Autor: | Justus C. Dachsel, Wen Lang Lin, Beate Winner, Matthew J. Farrer, Kenya Nishioka, Bahareh Behrouz, Sarah Lincoln, Joel E. Beevers, Brittany N. Dugger, Iryna Prots, Kelly M. Hinkle, Mei Yue, Erin E. Bowles, Dennis W. Dickson, Heather L. Melrose, Caroline Kent, Christopher Janus |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Aging
Parkinson's disease Dopamine Microdialysis lcsh:Geriatrics Neurodegenerative medicine.disease_cause Inbred C57BL Kidney lcsh:RC346-429 Mice 0302 clinical medicine Open-field 2.1 Biological and endogenous factors Aetiology Neuropathology Mice Knockout Neurons 0303 health sciences Mutation Behavior Animal Neurogenesis Dopaminergic Parkinson Disease Protein-Serine-Threonine Kinases LRRK2 Knockout mouse Neurological Research Article medicine.medical_specialty Medizinische Fakultät -ohne weitere Spezifikation Knockout Clinical Sciences Clinical Neurology Protein degradation Biology Protein Serine-Threonine Kinases Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 03 medical and health sciences Cellular and Molecular Neuroscience Internal medicine Behavioral and Social Science medicine Genetics Autophagy Animals ddc:610 Molecular Biology lcsh:Neurology. Diseases of the nervous system 030304 developmental biology Motor co-ordination Behavior Neurology & Neurosurgery Animal Wild type Neurosciences Kidney metabolism Brain Disorders nervous system diseases Mice Inbred C57BL lcsh:RC952-954.6 Endocrinology Parkinson’s disease Motor coordination Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Molecular Neurodegeneration Hinkle, KM; Yue, M; Behrouz, B; Dächsel, JC; Lincoln, SJ; Bowles, EE; et al.(2012). LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors. Molecular Neurodegeneration, 7(1). doi: 10.1186/1750-1326-7-25. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/4974v1qs Molecular neurodegeneration, vol 7, iss 1 Molecular Neurodegeneration, Vol 7, Iss 1, p 25 (2012) |
| DOI: | 10.14288/1.0215981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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