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

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...

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Autores principales: Devine, Michael J., Kaganovich, Alice, Ryten, Mina, Mamais, Adamantios, Trabzuni, Daniah, Manzoni, Claudia, McGoldrick, Philip, Chan, Diane, Dillman, Allissa, Zerle, Julia, Horan, Susannah, Taanman, Jan-Willem, Hardy, John, Marti-Masso, Jose-Felix, Healey, Daniel, Schapira, Anthony H., Wolozin, Benjamin, Bandopadhyay, Rina, Cookson, Mark R., van der Brug, Marcel P., Lewis, Patrick A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142158/
https://www.ncbi.nlm.nih.gov/pubmed/21799870
http://dx.doi.org/10.1371/journal.pone.0022489
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author Devine, Michael J.
Kaganovich, Alice
Ryten, Mina
Mamais, Adamantios
Trabzuni, Daniah
Manzoni, Claudia
McGoldrick, Philip
Chan, Diane
Dillman, Allissa
Zerle, Julia
Horan, Susannah
Taanman, Jan-Willem
Hardy, John
Marti-Masso, Jose-Felix
Healey, Daniel
Schapira, Anthony H.
Wolozin, Benjamin
Bandopadhyay, Rina
Cookson, Mark R.
van der Brug, Marcel P.
Lewis, Patrick A.
author_facet Devine, Michael J.
Kaganovich, Alice
Ryten, Mina
Mamais, Adamantios
Trabzuni, Daniah
Manzoni, Claudia
McGoldrick, Philip
Chan, Diane
Dillman, Allissa
Zerle, Julia
Horan, Susannah
Taanman, Jan-Willem
Hardy, John
Marti-Masso, Jose-Felix
Healey, Daniel
Schapira, Anthony H.
Wolozin, Benjamin
Bandopadhyay, Rina
Cookson, Mark R.
van der Brug, Marcel P.
Lewis, Patrick A.
author_sort Devine, Michael J.
collection PubMed
description 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.
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spelling pubmed-31421582011-07-28 Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue Devine, Michael J. Kaganovich, Alice Ryten, Mina Mamais, Adamantios Trabzuni, Daniah Manzoni, Claudia McGoldrick, Philip Chan, Diane Dillman, Allissa Zerle, Julia Horan, Susannah Taanman, Jan-Willem Hardy, John Marti-Masso, Jose-Felix Healey, Daniel Schapira, Anthony H. Wolozin, Benjamin Bandopadhyay, Rina Cookson, Mark R. van der Brug, Marcel P. Lewis, Patrick A. PLoS One Research Article 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. Public Library of Science 2011-07-22 /pmc/articles/PMC3142158/ /pubmed/21799870 http://dx.doi.org/10.1371/journal.pone.0022489 Text en 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. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Devine, Michael J.
Kaganovich, Alice
Ryten, Mina
Mamais, Adamantios
Trabzuni, Daniah
Manzoni, Claudia
McGoldrick, Philip
Chan, Diane
Dillman, Allissa
Zerle, Julia
Horan, Susannah
Taanman, Jan-Willem
Hardy, John
Marti-Masso, Jose-Felix
Healey, Daniel
Schapira, Anthony H.
Wolozin, Benjamin
Bandopadhyay, Rina
Cookson, Mark R.
van der Brug, Marcel P.
Lewis, Patrick A.
Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
title Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
title_full Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
title_fullStr Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
title_full_unstemmed Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
title_short Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
title_sort pathogenic lrrk2 mutations do not alter gene expression in cell model systems or human brain tissue
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142158/
https://www.ncbi.nlm.nih.gov/pubmed/21799870
http://dx.doi.org/10.1371/journal.pone.0022489
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