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Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue

Devine, MJ; Kaganovich, A; Ryten, M; Mamais, A; Trabzuni, D; Manzoni, C; ... Lewis, PA; + view all (2011) Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue. PLOS ONE , 6 (7) , Article e22489. 10.1371/journal.pone.0022489. Green and gold open access

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Abstract

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.

Type:Article
Title:Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
Open access status:An open access publication. A version is also available from UCL Discovery.
DOI:10.1371/journal.pone.0022489
Publisher version:http://dx.doi.org/10.1371/journal.pone.0022489
Language:English
Additional information:This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. This work was funded by the Medical Research Council (fellowship G0800437, MJD), Parkinson's UK (fellowship F-1002, PAL), Brain Research Trust and the Michael J. Fox foundation. It was supported in part by the Wellcome/MRC Parkinson's Disease Consortium grant and by the intramural program of the National Institute on Aging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords:PARKINSONS-DISEASE, PHOSPHORYLATION, PROTEINS, HEALTH, 4E-BP
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Clinical Neuroscience
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience

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