論文 - 詳細
| RRC ID | 86036 |
|---|---|
| 著者 | Perzel Mandell KA, Simmons SK, Nadig A, Farsi Z, Huang WC, Aryal S, Kwon MJ, Song B, Brenner K, Shepard N, Nicolella AA, O'Brien LD, Lichtman AH, Levin JZ, Sheng M. |
| タイトル | Meta-analysis of the brain transcriptomes of multiple genetic mouse models of schizophrenia highlights dysregulation in striatum and thalamus. |
| ジャーナル | Transl Psychiatry |
| Abstract |
Schizophrenia is a severe mental illness with high heritability, but its underlying mechanisms are poorly understood. We meta-analyzed large-scale brain transcriptomic data from mice harboring individual loss-of-function mutations in seven schizophrenia risk genes (Akap11, Dagla, Gria3, Grin2a, Sp4, Srrm2, Zmym2). While all studied brain regions were affected, the striatum and the thalamus emerged as key brain regions of convergence. Striatum showed downregulation of synapse- and oxidative phosphorylation-related gene sets in all models. In the thalamus, mutants separated into two groups based on transcriptomic phenotype: synapse-related gene sets were upregulated in mutants with only schizophrenia and bipolar association, and were downregulated in mutants that are associated with developmental delay/intellectual disability in addition to schizophrenia. Overall, our meta-analysis reveals convergence and divergence in brain transcriptomic phenotype in these schizophrenia genetic models, supports the involvement of striatal disturbance and synapse dysfunction in schizophrenia, and points to a key role of the thalamus. |
| 巻・号 | 15(1) |
| ページ | 345 |
| 公開日 | 2025-9-29 |
| DOI | 10.1038/s41398-025-03563-5 |
| PII | 10.1038/s41398-025-03563-5 |
| PMID | 41022686 |
| PMC | PMC12480767 |
| MeSH | Animals Corpus Striatum* / metabolism Corpus Striatum* / physiopathology Disease Models, Animal Mice Schizophrenia* / genetics Schizophrenia* / metabolism Thalamus* / metabolism Thalamus* / physiopathology Transcriptome* / genetics |
| IF | 5.28 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | RBRC02256 |