{"doi":"10.17615/arkq-3g85","title":"Cse1l Is a Negative Regulator of CFTR-Dependent Fluid Secretion","abstract":"Transport of chloride through the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel is a key step in regulating fluid secretion in vertebrates[1, 2]. Loss of CFTR function leads to cystic fibrosis (CF)[1, 3, 4], a disease that affects the lungs, pancreas, liver, intestine and vas deferens. Conversely, un-controlled activation of the channel leads to increased fluid secretion and plays a major role in several diseases and conditions including cholera[5, 6] and other secretory diarrheas [7] as well as Polycystic Kidney Disease (PKD)[8–10]. Understanding how CFTR activity is regulated in vivo has been limited by the lack of a genetic model. Here, we used a forward genetic approach in zebrafish to uncover CFTR regulators. We report the identification, isolation and characterization of a mutation in the zebrafish cse1l gene that leads to the sudden and dramatic expansion of the gut tube. We show that this phenotype results from a rapid accumulation of fluid due to the un-controlled activation of the CFTR channel. Analyses in zebrafish embryos and mammalian cells indicate that Cse1l is a negative regulator of CFTR-dependent fluid secretion. This work demonstrates the importance of fluid homeostasis in development and establishes the zebrafish as a much needed model system to study CFTR regulation in vivo.","journal":"UNC Libraries","year":2020,"id":139566,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"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":480595,"name":"Jan Huisken","orcid":"0000-0001-7250-3756","position":1,"is_corresponding":false},{"id":603083,"name":"Adam R. Navis","orcid":null,"position":2,"is_corresponding":false},{"id":603084,"name":"Koroboshka Brand‐Arzamendi","orcid":null,"position":3,"is_corresponding":false},{"id":603085,"name":"Silvia Curado","orcid":null,"position":4,"is_corresponding":false},{"id":307136,"name":"Michel Bagnat","orcid":"0000-0002-3829-0168","position":5,"is_corresponding":false},{"id":603086,"name":"Sara Herbstreith","orcid":null,"position":6,"is_corresponding":false},{"id":523368,"name":"Sherif E. Gabriel","orcid":null,"position":7,"is_corresponding":false},{"id":571214,"name":"Keith E. Mostov","orcid":"0000-0002-8123-6247","position":8,"is_corresponding":false},{"id":3242,"name":"Didier Y. R. Stainier","orcid":"0000-0002-0382-0026","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:10.185988Z","pmid":null,"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":[]}