{"doi":"10.1111/gbb.12725","title":"Generation and basic characterization of a gene‐trap knockout mouse model of <i>Scn2a</i> with a substantial reduction of voltage‐gated sodium channel Na<sub>v</sub>1.2 expression","abstract":"Abstract Large‐scale genetic studies revealed SCN2A as one of the most frequently mutated genes in patients with neurodevelopmental disorders. SCN2A encodes for the voltage‐gated sodium channel isoform 1.2 (Na v 1.2) expressed in the neurons of the central nervous system. Homozygous knockout (null) of Scn2a in mice is perinatal lethal, whereas heterozygous knockout of Scn2a ( Scn2a +/− ) results in mild behavior abnormalities. The Na v 1.2 expression level in Scn2a +/− mice is reported to be around 50–60% of the wild‐type (WT) level, which indicates that a close to 50% reduction of Na v 1.2 expression may not be sufficient to lead to major behavioral phenotypes in mice. To overcome this barrier, we characterized a novel mouse model of severe Scn2a deficiency using a targeted gene‐trap knockout (gtKO) strategy. This approach produces viable homozygous mice ( Scn2a gtKO/gtKO ) that can survive to adulthood, with about a quarter of Na v 1.2 expression compared to WT mice. Innate behaviors like nesting and mating were profoundly disrupted in Scn2a gtKO/gtKO mice. Notably, Scn2a gtKO/gtKO mice have a significantly decreased center duration compared to WT in the open field test, suggesting anxiety‐like behaviors in a novel, open space. These mice also have decreased thermal and cold tolerance. Additionally, Scn2a gtKO/gtKO mice have increased fix‐pattern exploration in the novel object exploration test and a slight increase in grooming, indicating a detectable level of repetitive behaviors. They bury little to no marbles and have decreased interaction with novel objects. These Scn2a gene‐trap knockout mice thus provide a unique model to study pathophysiology associated with severe Scn2a deficiency.","journal":"Genes Brain & Behavior","year":2020,"id":63884,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.941,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337743,"name":"Jingliang Zhang","orcid":"0000-0002-2903-1287","position":1,"is_corresponding":false},{"id":337744,"name":"Zhixiong Ma","orcid":"0000-0002-0088-8041","position":2,"is_corresponding":false},{"id":338571,"name":"Anthony C. Park","orcid":null,"position":3,"is_corresponding":false},{"id":337745,"name":"Emma E Lietzke","orcid":"0009-0005-5040-418X","position":4,"is_corresponding":false},{"id":338572,"name":"Chloé Maricela Romero","orcid":null,"position":5,"is_corresponding":false},{"id":338573,"name":"Yushuang Liu","orcid":null,"position":6,"is_corresponding":false},{"id":338574,"name":"Emily Rose Coleman","orcid":null,"position":7,"is_corresponding":false},{"id":337746,"name":"Xiaoling Chen","orcid":"0000-0002-2271-1140","position":8,"is_corresponding":false},{"id":337747,"name":"Tiange Xiao","orcid":"0000-0001-8579-832X","position":9,"is_corresponding":false},{"id":337748,"name":"Zhefu Que","orcid":"0000-0002-1358-0660","position":10,"is_corresponding":false},{"id":338575,"name":"Shirong Lai","orcid":null,"position":11,"is_corresponding":false},{"id":337749,"name":"Jiaxiang Wu","orcid":"0000-0002-1474-3820","position":12,"is_corresponding":false},{"id":338576,"name":"Ji Hea Lee","orcid":null,"position":13,"is_corresponding":false},{"id":338577,"name":"Sophia Palant","orcid":null,"position":14,"is_corresponding":false},{"id":338578,"name":"Huynhvi P. Nguyen","orcid":null,"position":15,"is_corresponding":false},{"id":337750,"name":"Zhuo Huang","orcid":"0000-0001-9198-4778","position":16,"is_corresponding":false},{"id":337751,"name":"William C. Skarnes","orcid":"0000-0002-8334-3329","position":17,"is_corresponding":false},{"id":337752,"name":"Wendy A. Koss","orcid":"0000-0002-2980-0672","position":18,"is_corresponding":false},{"id":337753,"name":"Yang Yang","orcid":"0000-0001-6417-3654","position":19,"is_corresponding":false},{"id":337742,"name":"Muriel Eaton","orcid":"0000-0002-8634-1214","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T21:11:24.000992Z","pmid":"33369088","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":[]}