{"doi":"10.1016/j.bpsgos.2025.100666","title":"Behavioral and Prefrontal Circuit Deficits in a Newly Developed Setbp1 Haploinsufficiency Mouse Model","abstract":"Background SET binding protein 1 ( SETBP1 ) regulates the cell cycle, gene transcription, and other vital intracellular processes. SETBP1 loss-of-function variants cause the neurodevelopmental disorders SETBP1 -haploinsufficiency disorder and SETBP1 related disorders ( SETBP1 -HD and SETBP1 -RD), characterized by attention-deficit / hyperactivity disorder, autism spectrum disorder, intellectual disability/developmental delay, and other neurological disabilities. Here we sought to characterize behavioral, physiological, and cell morphology phenotypes of a newly-developed mouse model of SETBP1 -HD. Methods We used open field, 3-chamber, Y-maze behavioral tests to measure activity, social interest, and spatial learning, respectively. We used whole cell current clamp recordings from medial prefrontal cortex layer 5 extratelencephalic projection neurons in ex-vivo slices to measure cell intrinsic and spike properties. We used morphological reconstruction to measure dendritic arborization in recorded neurons. Results Setbp1 +/- mice exhibited hyperactivity, decreased social interest, and increased olfactory exploration in behavioral tests. Ex vivo electrophysiology revealed hypoexcitability in layer 5 extratelencephalic projection neurons in the medial prefrontal cortex. Morphological reconstruction revealed changes to how branch points and length are distributed within the apical dendritic arbor of these prefrontal pyramidal neurons, without changes in overall length or branch number. Conclusions These data show that Setbp1 +/- mice exhibit phenotypes parallel to the attention-deficit / hyperactivity and autism spectrum disorder common in SETBP1 -HD patients. Additionally, we identified cellular changes to a key control center for attention, social behavior, and cognitive function that may elucidate the mechanism underlying the neuropsychiatric disabilities of this disorder.","journal":"Biological Psychiatry Global Open Science","year":2025,"id":537484,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"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":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1423719,"name":"Mendee A. Geist","orcid":null,"position":1,"is_corresponding":false},{"id":721650,"name":"Gregory J. Ordemann","orcid":"0000-0001-9755-7312","position":2,"is_corresponding":false},{"id":1423285,"name":"Alena Kizimenko","orcid":"0000-0001-5192-0112","position":3,"is_corresponding":false},{"id":1423720,"name":"Dominic M. Balice","orcid":null,"position":4,"is_corresponding":false},{"id":1185913,"name":"Fernando Isaac Guillén","orcid":"0009-0002-3871-604X","position":5,"is_corresponding":false},{"id":1423721,"name":"Emmanuella Bassey","orcid":null,"position":6,"is_corresponding":false},{"id":805136,"name":"Polina Lyuboslavsky","orcid":"0000-0002-7689-8537","position":7,"is_corresponding":false},{"id":345842,"name":"Audrey C. Brumback","orcid":"0000-0002-4904-4368","position":8,"is_corresponding":false},{"id":917221,"name":"MacKenzie A. Howard","orcid":"0000-0003-2832-6873","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:12.997494Z","pmid":"41640626","pmcid":null,"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":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}