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A CRISPR-Cas9 Gener...
A CRISPR-Cas9 Generated MDCK Cell Line Expressing Human MDR1 Without Endogenous Canine MDR1 (cABCB1) : An Improved Tool for Drug Efflux Studies.
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- Karlgren, Maria (författare)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab,Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Science for Life Laboratory
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- Simoff, Ivailo (författare)
- Uppsala universitet,Institutionen för farmaci
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- Backlund, Maria (författare)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab,Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Science for Life Laboratory
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- Wegler, Christine (författare)
- Uppsala universitet,Institutionen för farmaci,AstraZeneca
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- Keiser, Markus (författare)
- Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
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- Handin, Niklas (författare)
- Uppsala universitet,Institutionen för farmaci
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- Müller, Janett (författare)
- Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
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- Lundquist, Patrik (författare)
- Uppsala universitet,Institutionen för farmaci
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- Jareborg, Anne-Christine (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Oswald, Stefan (författare)
- Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
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- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab,Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Science for Life Laboratory
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- Engelska.
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 106:9, s. 2909-2913
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Madin-Darby canine kidney (MDCK) II cells stably transfected with transport proteins are commonly used models for drug transport studies. However, endogenous expression of especially canine MDR1 (cMDR1) confounds the interpretation of such studies. Here we have established an MDCK cell line stably overexpressing the human MDR1 transporter (hMDR1; P-glycoprotein), and used CRISPR-Cas9 gene editing to knockout the endogenous cMDR1. Genomic screening revealed the generation of a clonal cell line homozygous for a 4-nucleotide deletion in the canine ABCB1 gene leading to a frameshift and a premature stop codon. Knockout of cMDR1 expression was verified by quantitative protein analysis and functional studies showing retained activity of the human MDR1 transporter. Application of this cell line allowed unbiased reclassification of drugs previously defined as both substrates and non-substrates in different studies using commonly used MDCK-MDR1 clones. Our new MDCK-hMDR1 cell line, together with a previously developed control cell line, both with identical deletions in the canine ABCB1 gene and lack of cMDR1 expression represent excellent in vitro tools for use in drug discovery.
Nyckelord
- ABC transporters
- MDCK cells
- P-glycoprotein
- drug transport
- efflux pumps
- genomics
- membrane transporter
- multidrug resistance transporters
- permeability
- proteomics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Karlgren, Maria
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Simoff, Ivailo
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Backlund, Maria
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Wegler, Christin ...
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Keiser, Markus
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Handin, Niklas
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Müller, Janett
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Lundquist, Patri ...
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Jareborg, Anne-C ...
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Oswald, Stefan
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Artursson, Per
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Journal of Pharm ...
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Uppsala universitet