Evidence map›Paper›PMID 23748241›Full record

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.

Oliver T Parkinson, H Denny Liggitt, Allan E Rettie, Edward J Kelly

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.1field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Spotlight on CYP4B1.International journal of molecular sciences · 2023
    Review
  3. Assessing cytochrome P450 function using genetically engineered mouse models.Advances in pharmacology (San Diego, Calif.) · 2022
    Review
  4. Review
  5. Review
  6. Article
  7. ω-The Journal of biological chemistry · 2017
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Oliver T ParkinsonDepartment of Medicinal Chemistry, School of Pharmacy and Medicine,University of Washington, Seattle, Washington 98195-7610, USA.
H Denny Liggitt
Allan E Rettie
Edward J Kelly
Institute of Medicinal Plant Development · CNUniversity of Washington · US

Funding

XENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 1995 to 2026
$42.5M
MECHANISMS OF P450 DEPENDENT DESATURATIONR01GM049054 · NIGMS · UNIVERSITY OF WASHINGTON · PI RETTIE, ALLAN EDWARD · 1994 to 2010
$2.9M
NIEHS NIH HHS ES007033NIGMS NIH HHS GM49054NIGMS NIH HHS R01 GM049054
6 · The paper itself

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.

Indexed as

AnimalsAryl Hydrocarbon HydroxylasesBiotransformationKidneyLungMiceMice, Inbred C57BLMice, KnockoutReal-Time Polymerase Chain ReactionTerpenesToxins, Biological4-ipomeanolAryl Hydrocarbon Hydroxylasescytochrome P-450 CYP4B1TerpenesToxins, Biologicalcytochrome P450knockoutslungmetabolic activationpulmonary or respiratory system.

Identifiers

PMID23748241
PMCPMC3707440
OpenAlexW2100917338

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.