title: Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue.
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.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Devine
authors.forename: Alice
authors.initials: A
authors.lastname: Kaganovich
authors.forename: Mina
authors.initials: M
authors.lastname: Ryten
authors.forename: Adamantios
authors.initials: A
authors.lastname: Mamais
authors.forename: Daniah
authors.initials: D
authors.lastname: Trabzuni
authors.forename: Claudia
authors.initials: C
authors.lastname: Manzoni
authors.forename: Philip
authors.initials: P
authors.lastname: McGoldrick
authors.forename: Diane
authors.initials: D
authors.lastname: Chan
authors.forename: Allissa
authors.initials: A
authors.lastname: Dillman
authors.forename: Julia
authors.initials: J
authors.lastname: Zerle
authors.forename: Susannah
authors.initials: S
authors.lastname: Horan
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Taanman
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Jose-Felix
authors.initials: JF
authors.lastname: Marti-Masso
authors.forename: Daniel
authors.initials: D
authors.lastname: Healy
authors.forename: Daniel
authors.initials: D
authors.lastname: Healey
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Schapira
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolozin
authors.forename: Rina
authors.initials: R
authors.lastname: Bandopadhyay
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.forename: Marcel P
authors.initials: MP
authors.lastname: van der Brug
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Lewis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases