{"doi":"10.1038/s41398-025-03563-5","title":"Meta-analysis of the brain transcriptomes of multiple genetic mouse models of schizophrenia highlights dysregulation in striatum and thalamus","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.","journal":"Translational Psychiatry","year":2025,"id":527010,"datarank":0.21846513815862564,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.010520983990642026,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.010520983990642026,"corpus_percentile":37.1547922951961,"corpus_rank":8125,"citation_count":3,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6743,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":66.6667,"fair_percentile":86.48731274839498,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11078,"name":"Sean K. Simmons","orcid":"0000-0002-1537-4000","position":1,"is_corresponding":false},{"id":692494,"name":"Ajay Nadig","orcid":"0000-0001-9634-2141","position":2,"is_corresponding":false},{"id":1403133,"name":"Zohreh Farsi","orcid":"0000-0001-7274-981X","position":3,"is_corresponding":false},{"id":567308,"name":"Wei-Chao Huang","orcid":"0000-0003-0201-0985","position":4,"is_corresponding":false},{"id":574424,"name":"Sameer Aryal","orcid":"0000-0003-3577-4383","position":5,"is_corresponding":false},{"id":1403134,"name":"Min Jee Kwon","orcid":"0000-0002-1706-0806","position":6,"is_corresponding":false},{"id":583706,"name":"Bryan J. Song","orcid":"0000-0003-0549-4823","position":7,"is_corresponding":false},{"id":1403135,"name":"Kira Brenner","orcid":"0000-0001-6638-5300","position":8,"is_corresponding":false},{"id":1333208,"name":"Nate Shepard","orcid":"0000-0002-8629-3152","position":9,"is_corresponding":false},{"id":1403136,"name":"Ally Nicolella","orcid":"0000-0002-2175-6312","position":10,"is_corresponding":false},{"id":734132,"name":"Lesley D. Schurman","orcid":"0000-0002-5877-3976","position":11,"is_corresponding":false},{"id":284798,"name":"Aron H. Lichtman","orcid":"0000-0001-5601-985X","position":12,"is_corresponding":false},{"id":11089,"name":"Joshua Z. Levin","orcid":"0000-0002-0170-3598","position":13,"is_corresponding":false},{"id":287672,"name":"Morgan Sheng","orcid":"0000-0002-8703-5366","position":14,"is_corresponding":false},{"id":235988,"name":"Kira A. Perzel Mandell","orcid":"0000-0001-6262-6904","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:50:34.851930Z","pmid":"41022686","pmcid":"PMC12480767","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":83.3333,"fair_a":62.5,"fair_i":20.0,"fair_r":41.6667,"fair_zscore":1.2752,"fair_rationale":{"fair_score":66.67,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":83.33,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Data for Dagla mutants and substantia nigra data from Grin2a and Grin2b mutants has been uploaded to GEO at accession number GSE299704.","grounded":true,"rationale":"The paper provides a GEO accession (GSE299704), which is a persistent identifier scheme listed in the accepted set.","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"GEO","grounded":true,"rationale":"The paper names GEO as the repository where the data are deposited, which is a recognized data repository in the list.","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Data for Dagla mutants and substantia nigra data from Grin2a and Grin2b mutants has been uploaded to GEO at accession number GSE299704. 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