{"doi":"10.3390/biom14111397","title":"Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment","abstract":"The potassium sodium-activated channel subtype T member 1 (KCNT1) gene encodes the Slack channel KNa1.1, which is expressed in neurons throughout the brain. Gain-of-function variants in KCNT1 are associated with a spectrum of epilepsy syndromes, and mice carrying those variants exhibit a robust phenotype similar to that observed in patients. Kcnt1 knockout (KO) mice, however, have a normal lifespan without any epileptic phenotype. To understand the molecular differences between these two models, we conducted a comprehensive proteomic analysis of the cerebral cortices of Kcnt1 KO and Kcnt1R455H/+ mice, an animal model bearing a cytoplasmic C-terminal mutation homologous to a human R474H variant that results in EIMFS. The greatest change observed in Kcnt1 KO mice compared to the wild-type mice was the increased expression of multiple proteins of the inner mitochondrial membrane. Electron microscopy studies of cortical mitochondria from Kcnt1 KO mice further confirmed a significant increase in the density of mitochondrial cristae compared to that in wild-type mice. Kcnt1 reduction by a murine-specific Kcnt1 antisense oligonucleotide (ASO) in Kcnt1R455H/+ mice partially corrected the proteomic dysregulations in the disease model. The results support the hypothesis that ASO-mediated KCNT1 reduction could be therapeutically useful in the treatment of KCNT1 epilepsies.","journal":"Biomolecules","year":2024,"id":461586,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9439,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":646038,"name":"Huafeng Wang","orcid":"0000-0002-7326-4379","position":1,"is_corresponding":false},{"id":271582,"name":"Jing Wu","orcid":"0000-0003-3479-5561","position":2,"is_corresponding":false},{"id":355251,"name":"Imran H. Quraishi","orcid":"0000-0003-2859-7446","position":3,"is_corresponding":false},{"id":1063790,"name":"Yalan Zhang","orcid":"0000-0003-3185-2305","position":4,"is_corresponding":false},{"id":1291085,"name":"Maysam Pedram","orcid":null,"position":5,"is_corresponding":false},{"id":1290517,"name":"Benbo Gao","orcid":"0000-0003-4247-3706","position":6,"is_corresponding":false},{"id":271589,"name":"Elizabeth A. Jonas","orcid":"0000-0002-1624-5999","position":7,"is_corresponding":false},{"id":890807,"name":"Viet Nguyen","orcid":"0000-0001-6867-6929","position":8,"is_corresponding":false},{"id":1290518,"name":"Sijia Wu","orcid":"0000-0001-5729-3973","position":9,"is_corresponding":false},{"id":446061,"name":"Omar S. Mabrouk","orcid":"0000-0001-5325-1944","position":10,"is_corresponding":false},{"id":262353,"name":"Paymaan Jafar‐Nejad","orcid":"0000-0001-5176-739X","position":11,"is_corresponding":false},{"id":355257,"name":"Leonard K. Kaczmarek","orcid":"0000-0001-5128-6326","position":12,"is_corresponding":false},{"id":1290516,"name":"Fangxu Sun","orcid":"0000-0003-0773-881X","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:04:16.410510Z","pmid":"39595574","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":[]}