Parkinson Phenotype in Aged PINK1-Deficient Mice Is Accompanied by Progressive Mitochondrial Dysfunction in Absence of Neurodegeneration
Transcriptomics Dataset
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General Information
AccessionGSE60413
TitleParkinson Phenotype in Aged PINK1-Deficient Mice Is Accompanied by Progressive Mitochondrial Dysfunction in Absence of Neurodegeneration
DescriptionParkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD. Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of -synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. Thus, aging Pink1/ mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Transcriptome microarray data of Pink1-/- mouse brains in absence of a stressor, even at old age, show remarkably sparse dysregulations. See Gispert-S et al 2009 PLOS ONE.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60413
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Keyword
Dataset Accession

Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset

Dataset Accession
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Geneset

Small molecules which mimic PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse PINK1 KO
The L1000 database was queried in order to identify small molecule perturbations which rev...
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