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Series GSE16223 Query DataSets for GSE16223
Status Public on Jan 08, 2010
Title Prionic protein gene dosage is critical for maintenance of neuronal homeostasis of hippocampal circuits
Organism Mus musculus
Experiment type Expression profiling by array
Summary We demonstrate that Prnp dosage is critical for the maintenance of neuronal homeostasis since both its absence and, more relevantly, its overexpression induce higher sensitivity to kainate (KA) damage. These data correlate with electrophysiological results in freely behaving mutant mice showing an imbalance in activity-dependent synaptic processes, as determined from input/output curves, paired-pulse facilitation, and LTP studies. Gene expression profiling showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission among others were co-regulated in knockout and PrPc overexpressing mice. RT-qPCR analysis of neurotransmission-related genes confirmed GABA-A and AMPA-Kainate receptor subunit transcriptional co-regulation in both Prnp -/- and Tg20 mice. Our results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its interactions with GABAA and AMPA-Kainate receptors.

Keywords: steady state expression; adult brain tissue; hippocampus; genetic modification; transgenic gain of function mutation; targetted deletion loss of function mutation
 
Overall design We performed a global transcriptome analysis of three strains that differ in their Prnp gene dose using Illumina Sentrix 6 mouse v1.1 beadarrays. We analyzed mRNA expression in the hippocampi of four individual male mice from each of three strains: 1) Tg20, with a 30 exogenous copies of the Prnp gene within a Prnp -/- background that overexpresses PrPc about 6-7 times the normal wild type levels; 2) littermates lacking the transgene and therefore carrying only the homozygous knock out Prnp -/- strain which lacks expression of PrPc; and 3) their wild type counterparts carrying two copies of the intact Prnp gene and expressing normal levels of PrPc
 
Contributor(s) Del Rio JA, Rangel A, Sumoy L
Citation(s) 19855845
Submission date May 26, 2009
Last update date Jan 18, 2013
Contact name Lauro Sumoy
E-mail(s) lsumoy@igtp.cat
Organization name IGTP
Department High Content Genomics and Bioinformatics
Street address Ctra. Can Ruti, Camí de les escoles s/n
City Badalona
State/province Barcelona
ZIP/Postal code 08916
Country Spain
 
Platforms (1)
GPL6105 Illumina mouse-6 v1.1 expression beadchip
Samples (12)
GSM407360 Prnp Tg20 repl1
GSM407361 Prnp Tg20 repl2
GSM407362 Prnp Tg20 repl3
Relations
BioProject PRJNA117167

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE16223_RAW.tar 5.2 Mb (http)(custom) TAR
GSE16223_raw.txt.gz 12.6 Mb (ftp)(http) TXT
Processed data included within Sample table

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