Evidence map›Paper›PMID 28218310›Full record

ArticleScientific reports2017

CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug metabolism and pharmacokinetics research.

Jian Lu, Yanjiao Shao, Xuan Qin, Daozhi Liu, Ang Chen, Dali Li, Mingyao Liu, Xin Wang

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

16 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Pharmaceuticals (Basel, Switzerland) · 2023
    Article
  3. Article
  4. Review
  5. Recent Advances in the Production of Genome-Edited Rats.International journal of molecular sciences · 2022
    Review
  6. Review
  7. Review
  8. Article
  9. Effect of You-Gui Yin on the Activities of Seven Cytochrome P450 Isozymes in Rats.Evidence-based complementary and alternative medicine : eCAM · 2020
    Article
  10. Using CRISPR/Cas9 to model human liver disease.JHEP reports : innovation in hepatology · 2019
    Review
  11. Review
  12. Role of vitamin D receptor in the regulation ofActa pharmaceutica Sinica. B · 2019
    Review
  13. Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  14. Review
  15. CRISPR/Cas9 Genetic Modification ofDrug metabolism and disposition: the biological fate of chemicals · 2017
    Article
  16. 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

8 authors at 2 institutions in 2 countries.

Jian LuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Yanjiao ShaoShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Xuan QinShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Daozhi LiuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Ang ChenShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Dali LiShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Mingyao LiuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Xin WangShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
East China Normal University · CNTexas A&M Health Science Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytochrome P450 (CYP) 3A accounts for nearly 30% of the total CYP enzymes in the human liver and participates in the metabolism of over 50% of clinical drugs. Moreover, CYP3A plays an important role in chemical metabolism, toxicity, and carcinogenicity. New animal models are needed to investigate CYP3A functions, especially for drug metabolism. In this report, Cyp3a1/2 double knockout (KO) rats were generated by CRISPR-Cas9 technology, and then were characterized for viability and physiological status. The Cyp3a1/2 double KO rats were viable and fertile, and had no obvious physiological abnormities. Compared with the wild-type (WT) rat, Cyp3a1/2 expression was completely absent in the liver of the KO rat. In vitro and in vivo metabolic studies of the CYP3A1/2 substrates indicated that CYP3A1/2 was functionally inactive in double KO rats. The Cyp3a1/2 double KO rat model was successfully generated and characterized. The Cyp3a1/2 KO rats are a novel rodent animal model that will be a powerful tool for the study of the physiological and pharmacological roles of CYP3A, especially in drug and chemical metabolism in vivo.

Indexed as

AnimalsCRISPR-Cas SystemsCytochrome P-450 CYP3AFemaleGenotypeHalf-LifeIntestine, SmallLiverMaleMicrosomes, LiverNifedipinePhenotypeProtein IsoformsRatsRats, Sprague-DawleyCyp3a23-3a1 protein, ratCyp3a2 protein, ratCytochrome P-450 CYP3ANifedipineProtein Isoforms

Identifiers

PMID28218310
PMCPMC5317174
OpenAlexW2589738668

What OpenQuestion holds

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Registered trials

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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.