{"doi":"10.1371/journal.pone.0335854","title":"A porcine model of Fanconi anemia","abstract":"Although small animal models of Fanconi anemia (FA) are useful, they do not faithfully replicate many of the clinical features seen in FA patients. We reasoned that a porcine model of FA with its similar physiology and a relatively long lifespan would produce a phenotype more similar to human FA. Targeting FANCA in domestic swine resulted in skeletal abnormalities and extreme sensitivity to interstrand DNA cross-linking agents. In addition, FANCA disruption followed by mitomycin C treatment resulted in a > 10-fold increase in chromosomal radials, a finding that is considered diagnostic for human FA. Bone marrow derived, hematopoietic progenitor cells from a FANCA null pig showed a 75% reduction in colony forming activity compared to wild type. Evaluation of steady state hematopoiesis in the peripheral blood revealed the gradual development of red cell macrocytosis and a reduction in circulating neutrophils. Targeting of FANCD2 failed to produce any biallelic animals demonstrating the loss of FANCD2 function is embryonic lethal in pigs. These results indicate that a porcine model of FANCA holds promise for the development of strategies to prevent the development of bone marrow failure and malignancies in patients with FA.","journal":"PLoS ONE","year":2025,"id":579657,"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":0.9516,"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":465064,"name":"Kristin M. Whitworth","orcid":"0000-0001-9959-108X","position":1,"is_corresponding":false},{"id":343946,"name":"Devorah C. Goldman","orcid":"0000-0002-5667-5600","position":2,"is_corresponding":false},{"id":292829,"name":"Lisa A. Moreau","orcid":"0000-0003-2985-0415","position":3,"is_corresponding":false},{"id":343948,"name":"Kelsey McQueen","orcid":"0000-0002-2448-0200","position":4,"is_corresponding":false},{"id":35833,"name":"Kalindi Parmar","orcid":"0000-0002-9522-1716","position":5,"is_corresponding":false},{"id":7163,"name":"Alan D. D’Andrea","orcid":"0000-0001-6168-6294","position":6,"is_corresponding":false},{"id":454693,"name":"Melissa Samuel","orcid":"0000-0002-1416-7835","position":7,"is_corresponding":false},{"id":454694,"name":"Kevin D. Wells","orcid":"0000-0002-9386-0004","position":8,"is_corresponding":false},{"id":393506,"name":"Randall S. Prather","orcid":"0000-0002-6012-4035","position":9,"is_corresponding":false},{"id":1490589,"name":"Craig Dorell","orcid":null,"position":10,"is_corresponding":false},{"id":279344,"name":"Markus Grompe","orcid":"0000-0002-6616-4345","position":11,"is_corresponding":false},{"id":176315,"name":"William H. Fleming","orcid":null,"position":12,"is_corresponding":false},{"id":1490588,"name":"Brandon Hergert","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:58:34.718602Z","pmid":"41171815","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":[]}