E-GEOD-13033 - Transcription profiling of mouse brain tissue from HtrA2 knockouts

Status
Submitted on 3 October 2008, released on 13 January 2009, last updated on 10 June 2011
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (5)
Description
Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinson’s disease patients’ brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases. Experiment Overall Design: This experiment was set out to identify genes that are differentially expressed in brain tissue from the cortex of HtrA2 knockout (KO) mice compared to wild type (WT) littermates. We chose a cortical region since there is no evidence of neuronal loss in this region enabling us to compare mRNA transcripts in identical cellular populations. Brains of littermate WT and HtrA2 KO mice were dissected to obtain cortex tissue at post-natal day 29 (P29). RNA was isolated and samples were processed for hybridisation (6 samples in total, 3 replicates for each genotype).
Experiment types
transcription profiling by array, unknown experiment type
Contact
Kristina Klupsch
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-13033.idf.txt
Sample and data relationshipE-GEOD-13033.sdrf.txt
Raw data (1)E-GEOD-13033.raw.1.zip
Processed data (1)E-GEOD-13033.processed.1.zip
Array designA-AFFY-45.adf.txt
R ExpressionSetE-GEOD-13033.eSet.r
Links