ArticlePharmaceutical research2015
Genomic Knockout of Endogenous Canine P-Glycoprotein in Wild-Type, Human P-Glycoprotein and Human BCRP Transfected MDCKII Cell Lines by Zinc Finger Nucleases.
Article in Pharmaceutical research, 2015. 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, 31 citations in OpenAlex.
- The pH-dependence of efflux ratios determined with bidirectional transport assays across cellular monolayers.International journal of pharmaceutics: X · 2024Article
- Knockout Transporter Cell Lines to Assess Substrate Potential Towards Efflux Transporters.The AAPS journal · 2024Article
- Interlaboratory Variability in the Madin-Darby Canine Kidney Cell Proteome.Molecular pharmaceutics · 2023Article
- Improvement of Workflows and Assay Reproducibility by The Introduction of "Assay-Ready" Culturing of MDCK Cells for Transport Studies.Pharmaceutical research · 2023Article
- A Unique In Vitro Assay to Investigate ABCB4 Transport Function.International journal of molecular sciences · 2023Article
- CRISPR/Cas9 targeting liposomes knocked down multidrug resistance proteins in brain endothelial cells as a model to predict potential pharmacoresistance.Colloids and surfaces. B, Biointerfaces · 2023Article
- P-Glycoprotein (MDR1/ABCB1) Restricts Brain Accumulation of the Novel EGFR Inhibitor EAI045 and Oral Elacridar Coadministration Enhances Its Brain Accumulation and Oral Exposure.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development.Acta pharmaceutica Sinica. B · 2022Review
- Potential and Limits of Kidney Cells for Evaluation of Renal Excretion.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Characterization and Validation of Canine P-Glycoprotein-Deficient MDCK II Cell Lines for Efflux Substrate Screening.Pharmaceutical research · 2020Article
- IPEC-J2 rMdr1a, a New Cell Line with Functional Expression of Rat P-glycoprotein Encoded by Rat Mdr1a for Drug Screening Purposes.Pharmaceutics · 2020Article
- Revisiting atenolol as a low passive permeability marker.Fluids and barriers of the CNS · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate whether it is possible to specifically suppress the expression and function of endogenous canine P-glycoprotein (cPgp) in Madin-Darby canine kidney type II cells (MDCKII) transfected with hPGP and breast cancer resistance protein (hBCRP) by zinc finger nuclease (ZFN) producing sequence specific DNA double strand breaks.
methodsWild-type, hPGP-transfected, and hBCRP-transfected MDCKII cells were transfected with ZFN targeting for cPgp. Net efflux ratios (NER) of Pgp and Bcrp substrates were determined by dividing efflux ratios (basal-to-apical / apical-to-basal) in over-expressing cell monolayers by those in wild-type ones.
resultsFrom ZFN-transfected cells, cell populations (ko-cells) showing knockout of cPgp were selected based on genotyping by PCR. qRT-PCR analysis showed the significant knock-downs of cPgp and interestingly also cMrp2 expressions. Specific knock-downs of protein expression for cPgp were shown by western blotting and quantitative targeted absolute proteomics. Endogenous canine Bcrp proteins were not detected. For PGP-transfected cells, NERs of 5 Pgp substrates in ko-cells were significantly greater than those in parental cells not transfected with ZFN. Similar result was obtained for BCRP-transfected cells with a dual Pgp and Bcrp substrate.
conclusionSpecific efflux mediated by hPGP or hBCRP can be determined with MDCKII cells where cPgp has been knocked out by ZFN.
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