{"doi":"10.1021/ehp.6c00312","title":"A New Mouse Model for Ozone Health Effects Research","abstract":"BACKGROUND: Exposure to the ambient air pollutant ozone (O 3 ) is associated with adverse respiratory health outcomes. Rodent models have been used to identify mechanisms of response to O 3, but their utility has been questioned owing to species differences in physiologic response, most notably exposure-induced hypothermia, which renders rodents relatively resistant to O 3 compared to humans. OBJECTIVES: First, to test whether a recombinant inbred mouse strain from the Collaborative Cross population, CC002/Unc, provides a sensitive model of ozone response by benchmarking it to the most commonly used inbred strain, C57BL/6J. Second, to identify the genetic basis of CC002/Unc’s sensitivity. METHODS: We examined the responses of CC002/Unc and C57BL/6J mice to either acute (0.4 or 0.8 ppm O 3 4 h) or repeated (0.8 ppm O 3 × 4 h/day × 3 or 9 weekdays) O 3 exposure. Then, we mapped quantitative trait loci (QTL) for responses to 9 days of O 3 in a CC002/Unc × CC005/TauUnc (O 3 -resistant) backcross population. RESULTS: CC002/Unc was far more responsive to acute O 3 than C57BL/6J, exhibiting significant inflammation following a single 0.4 ppm O 3 exposure and greater inflammation and injury after 0.8 ppm O 3 . Enhanced sensitivity of CC002/Unc mice was associated with decreased breathing frequency and diminished hypothermic responses. Following repeated exposure, C57BL/6J lungs appeared normal, while CC002/Unc lungs had eosinophilic inflammation and centriacinar fibrosis. We identified five QTL for airway eosinophilia, including a large-effect QTL on chromosome 11 that accounts for 18% of phenotypic variation and contains genes with plausible links to aberrant immune responses. DISCUSSION: The CC002/Unc strain provides an improved model to study the effects of acute and repeated O 3 exposure due to its enhanced sensitivity vs C57BL/6J and more human-like thermoregulatory response. Further genetic analysis to pinpoint causal genes underlying CC002/Unc’s susceptibility will provide new insights into mechanisms of O 3 -induced lung disease.","journal":"Environmental Health Perspectives","year":2025,"id":567591,"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":0.9257,"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":55079,"name":"Robert M. Immormino","orcid":"0000-0003-1998-1307","position":1,"is_corresponding":false},{"id":275086,"name":"Martin T. Ferris","orcid":"0000-0003-1241-6268","position":2,"is_corresponding":false},{"id":997236,"name":"Sarah Lester","orcid":"0000-0002-6230-6350","position":3,"is_corresponding":false},{"id":370703,"name":"Timothy P. Moran","orcid":"0000-0002-6832-9772","position":4,"is_corresponding":false},{"id":313892,"name":"Jack R. Harkema","orcid":"0000-0003-4682-0824","position":5,"is_corresponding":false},{"id":570717,"name":"Samir N. P. Kelada","orcid":"0000-0003-2676-9232","position":6,"is_corresponding":false},{"id":535476,"name":"Gregory J. Smith","orcid":"0000-0002-5305-0445","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T02:56:48.183032Z","pmid":"40471753","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":[]}