論文 - 詳細
| RRC ID | 11779 |
|---|---|
| 著者 | Labrie V, Fukumura R, Rastogi A, Fick LJ, Wang W, Boutros PC, Kennedy JL, Semeralul MO, Lee FH, Baker GB, Belsham DD, Barger SW, Gondo Y, Wong AH, Roder JC. |
| タイトル | Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model. |
| ジャーナル | Hum Mol Genet |
| Abstract |
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. |
| 巻・号 | 18(17) |
| ページ | 3227-43 |
| 公開日 | 2009-9-1 |
| DOI | 10.1093/hmg/ddp261 |
| PII | ddp261 |
| PMID | 19483194 |
| PMC | PMC2722985 |
| MeSH | Animals Case-Control Studies Disease Models, Animal Disease Susceptibility* Female Humans Male Mice Mice, Inbred Strains Mutation Pedigree Racemases and Epimerases / genetics Racemases and Epimerases / metabolism* Schizophrenia / enzymology* Schizophrenia / genetics Schizophrenia / physiopathology Serine / metabolism |
| IF | 5.101 |
| 引用数 | 115 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRCGD000099 |