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Series GSE97198 Query DataSets for GSE97198
Status Public on Mar 30, 2017
Title RNA expression across 6 strains of mice in relation to prepulse inhibition testing, as described in: Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1) modulates pre-pulse inhibition of acoustic startle in the mouse
Organism Mus musculus
Experiment type Expression profiling by array
Summary C3H/HeJ, BalbC/J, C57BL/6J, C57BL10/J, C57BLKS/J, C57L/J strains were tested for variability in gene expression in hippocampus, striatal, and brainstem tissues to affiliate findings with behavioural prepulse inhibition scores
Abstract: Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic pre-pulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains. We examined several brain regions involved in PPI and schizophrenia: hippocampus, striatum and brainstem, and found transcripts that had good correlation with PPI level, and confirmed this with real-time quantitative PCR. We then selected one candidate gene for further study, Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1), because it is a putative enzyme that could metabolize catecholamine neurotransmitters, and thus might be a feasible target for new medications. We determined that Pdxdc1 mRNA and protein are both strongly expressed in the hippocampus and levels of Pdxdc1 are inversely correlated with PPI across the six mouse strains. Using shRNA packaged in a lentiviral vector, we suppressed Pdxdc1 protein levels in the hippocampus and increased PPI by at least 16%. Our results suggest that Pdxdc1 may regulate PPI and could be investigated further as a potential treatment target for schizophrenia.
 
Overall design 18 arrays were sampled per tissue type, 3 arrays per strain of mice, two of which were from control mice (untested for PPI) and one from PPI tested mice, each array had pooled tissue from 3 mice from the experimental group, from alternating hemispheres (e.g. 2 tissue samples from right, 1 from left, and vice versa to balance the whole 3-array set from each strain). 3 tissue types were tested: brainstem, hippocampus, and striatum.
 
Contributor(s) Feldcamp L, Boutros P, Raymond R, J.Fletcher P, Nobrega JN, Wong AH
Citation(s) 28485732
Submission date Mar 29, 2017
Last update date Feb 11, 2019
Contact name James Nicholas Samsom
Organization name University of Toronto
Department Pharmacology
Lab Wong Lab
Street address 544, 155 Dalhousie Street
City Toronto
State/province Ontario
ZIP/Postal code M5B2P7
Country Canada
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (54)
GSM2559520 hippocampus ppi tested C3H HeJ biological replicate 1
GSM2559521 hippocampus ppi untested C3H HeJ biological replicate 1
GSM2559522 hippocampus ppi untested C3H HeJ biological replicate 2
Relations
BioProject PRJNA380935

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

Supplementary file Size Download File type/resource
GSE97198_RAW.tar 226.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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