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1552925 
Journal Article 
Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model 
Labrie, V; Fukumura, R; Rastogi, A; Fick, LJ; Wang, Wei; Boutros, PC; Kennedy, JL; Semeralul, MO; Lee, FH; Baker, GB; Belsham, DD; Barger, SW; Gondo, Y; Wong, AHC; Roder, JC 
2009 
Yes 
Human Molecular Genetics
ISSN: 0964-6906
EISSN: 1460-2083 
18 
17 
3227-3243 
19483194 
WOS:000268807300008 
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 dramatically reduced d-serine levels. Mutant mice displayed behaviors relevant to schizophrenia, including impairments in prepulse inhibition, sociability and spatial discrimination. Behavioral deficits were exacerbated by an NMDAR antagonist and ameliorated by d-serine or the atypical antipsychotic clozapine. Expression profiling revealed that the Srr mutation influenced several genes that have been linked to schizophrenia and cognitive ability. Transcript levels altered by the Srr mutation were also normalized by d-serine or clozapine treatment. Furthermore, analysis of SRR genetic variants in humans identified a robust association with schizophrenia. This study demonstrates that aberrant Srr function and diminished d-serine may contribute to schizophrenia pathogenesis.