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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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022489&type=printable |
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| author | Michael J Devine Alice Kaganovich Mina Ryten Adamantios Mamais Daniah Trabzuni Claudia Manzoni Philip McGoldrick Diane Chan Allissa Dillman Julia Zerle Susannah Horan Jan-Willem Taanman John Hardy Jose-Felix Marti-Masso Daniel Healy Anthony H Schapira Benjamin Wolozin Rina Bandopadhyay Mark R Cookson Marcel P van der Brug Patrick A Lewis |
| author_facet | Michael J Devine Alice Kaganovich Mina Ryten Adamantios Mamais Daniah Trabzuni Claudia Manzoni Philip McGoldrick Diane Chan Allissa Dillman Julia Zerle Susannah Horan Jan-Willem Taanman John Hardy Jose-Felix Marti-Masso Daniel Healy Anthony H Schapira Benjamin Wolozin Rina Bandopadhyay Mark R Cookson Marcel P van der Brug Patrick A Lewis |
| author_sort | Michael J Devine |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-c6fe6ed743ea4ec3bf74262e0c03b0ea |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c6fe6ed743ea4ec3bf74262e0c03b0ea2025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2248910.1371/journal.pone.0022489Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue.Michael J DevineAlice KaganovichMina RytenAdamantios MamaisDaniah TrabzuniClaudia ManzoniPhilip McGoldrickDiane ChanAllissa DillmanJulia ZerleSusannah HoranJan-Willem TaanmanJohn HardyJose-Felix Marti-MassoDaniel HealyAnthony H SchapiraBenjamin WolozinRina BandopadhyayMark R CooksonMarcel P van der BrugPatrick A LewisPoint 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022489&type=printable |
| spellingShingle | Michael J Devine Alice Kaganovich Mina Ryten Adamantios Mamais Daniah Trabzuni Claudia Manzoni Philip McGoldrick Diane Chan Allissa Dillman Julia Zerle Susannah Horan Jan-Willem Taanman John Hardy Jose-Felix Marti-Masso Daniel Healy Anthony H Schapira Benjamin Wolozin Rina Bandopadhyay Mark R Cookson Marcel P van der Brug Patrick A Lewis Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022489&type=printable |
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