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| 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
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| 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
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| Overall design |
Four wild-type and four SRR mice were analyzed for each of three brain regions (cerebellum, hippocampus, and frontal cortex).
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| 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 |
| E-mail(s) |
Paul.Boutros@utoronto.ca
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| Organization name |
Ontario Institute for Cancer Research
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| Street address |
101 College Street, Suite 800
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA110227 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE13974_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of TIFF, TXT) |
| Processed data included within Sample table |
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