{"doi":"10.1101/2023.10.27.564474","title":"Characterization of an <i>Osmr</i> Conditional Knockout Mouse Model","abstract":"ABSTRACT Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines and has been found to have distinct anti-inflammatory and pro-inflammatory properties in various cellular and disease contexts. OSM signals through two receptor complexes, one of which includes OSMRβ. To investigate OSM-OSMRβ signaling in adult hematopoiesis, we utilized the readily available conditional Osmr fl/fl mouse model B6;129- Osmr tm1 . 1Nat /J, which is poorly characterized in the literature. This model contains loxP sites flanking exon 2 of the Osmr gene. We crossed Osmr fl/fl mice to interferon-inducible Mx1 -Cre, which is robustly induced in adult hematopoietic cells. We observed complete recombination of the Osmr fl allele and loss of exon 2 in hematopoietic (bone marrow) as well as non-hematopoietic (liver, lung, kidney) tissues. Using a TaqMan assay with probes downstream of exon 2, Osmr transcript was lower in the kidney but equivalent in bone marrow, lung, and liver from Osmr fl/fl Mx1 -Cre versus Mx1 -Cre control mice, suggesting that transcript is being produced despite loss of this exon. Western blots show that liver cells from Osmr fl/fl Mx1 -Cre mice had complete loss of OSMR protein, while bone marrow, kidney, and lung cells had reduced OSMR protein at varying levels. RNA-seq analysis of a subpopulation of bone marrow cells (hematopoietic stem cells) finds that some OSM-stimulated genes, but not all, are suppressed in Osmr fl/fl Mx1 -Cre cells. Together, our data suggest that the B6;129- Osmr tm1 . 1Nat /J model should be utilized with caution as loss of Osmr exon 2 has variable and tissue-dependent impact on mRNA and protein expression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":413459,"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":0.9289,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":520348,"name":"Ruth L. Saxl","orcid":null,"position":1,"is_corresponding":false},{"id":572381,"name":"Timothy M. Stearns","orcid":"0000-0002-5533-6076","position":2,"is_corresponding":false},{"id":302104,"name":"Jennifer J. Trowbridge","orcid":"0000-0002-7636-9504","position":3,"is_corresponding":false},{"id":534700,"name":"Logan S. Schwartz","orcid":"0000-0001-6724-0787","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:21:57.641539Z","pmid":"37961653","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":[]}