ArticleToxicological sciences : an official journal of the Society of Toxicology2013
Generation and characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of Ipomeanol.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Functional analysis of CYP4B1 enzymes from apes and humans uncovers evolutionary hot spots for adaptations of the catalytical function.PLoS genetics · 2025Article
- Spotlight on CYP4B1.International journal of molecular sciences · 2023Review
- Assessing cytochrome P450 function using genetically engineered mouse models.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- Metabolic Activation of the Toxic Natural Products From Herbal and Dietary Supplements Leading to Toxicities.Frontiers in pharmacology · 2021Review
- Xenobiotic metabolism in differentiated human bronchial epithelial cells.Archives of toxicology · 2017Article
- ω-The Journal of biological chemistry · 2017Article
- Ligand characterization of CYP4B1 isoforms modified for high-level expression in Escherichia coli and HepG2 cells.Protein engineering, design & selection : PEDS · 2017Article
- Species Differences in Microsomal Oxidation and Glucuronidation of 4-Ipomeanol: Relationship to Target Organ Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Identification of amino acid determinants in CYP4B1 for optimal catalytic processing of 4-ipomeanol.The Biochemical journal · 2015Article
- Generation and characterization of a murine model of Bietti crystalline dystrophy.Investigative ophthalmology & visual science · 2014Article
- Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition.Drug metabolism reviews · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 (-/-) mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 (-/-) mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 (+/+) animals. Administration of IPO (20mg/kg) to Cyp4b1 (+/+) mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 (-/-) mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 (-/-) mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.