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Series GSE13974 Query DataSets for GSE13974
Status Public on Sep 05, 2009
Title Genetic inactivation of serine racemase produces behavioral phenotypes related to schizophrenia in mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Abnormal N-methyl-D-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. D-serine is an important NMDAR modulator, and to elucidate the role of the D-serine synthesis enzyme serine racemase (Srr) in schizophrenia, we identified and characterized mice with an ENU-induced mutation that results in a complete loss of Srr activity and drastically reduced D-serine levels. Mutant mice displayed behaviors relevant to schizophrenia, including impairments in prepulse inhibition, sociability and spatial discrimination. Behavioral deficits were rescued by D-serine and the atypical antipsychotic clozapine, and were conversely, amplified by NMDAR inhibition. Expression profiling revealed that the Srr mutation influenced several genes that have been linked to schizophrenia and cognitive ability. Furthermore, analysis of Srr genetic variants in humans identified a robust association with schizophrenia. This study demonstrates that aberrant serine racemase function and diminished D-serine may contribute to schizophrenia pathogenesis, and that D-serine may be a beneficial form of treatment

Keywords: genetic-mutant vs. wildtype comparison
Overall design Four wild-type and four SRR mice were analyzed for each of three brain regions (cerebellum, hippocampus, and frontal cortex).
Contributor(s) Labrie V, Fukumura R, Rastogi A, Fick LJ, Wei W, Boutros PC, Semeralul MO, Lee FH, Baker GB, Belsham DD, Barger SW, Gondo Y, Wong AH, Roder JC
Citation(s) 19483194
Submission date Dec 15, 2008
Last update date Jun 14, 2018
Contact name Paul C Boutros
Organization name Ontario Institute for Cancer Research
Street address 101 College Street, Suite 800
City Toronto
State/province Ontario
ZIP/Postal code M5G 0A3
Country Canada
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (24)
GSM351169 Cerebellum-SRRmutant-rep1
GSM351170 Cerebellum-SRRmutant-rep2
GSM351171 Cerebellum-SRRmutant-rep3
BioProject PRJNA110227

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
GSE13974_RAW.tar 1.5 Gb (http)(custom) TAR (of TIFF, TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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