Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9 Ivailo Simoff, Maria Karlgren, Maria Backlund, Anne-Christine Lindström, Fabienne.

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Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9 Ivailo Simoff, Maria Karlgren, Maria Backlund, Anne-Christine Lindström, Fabienne Z. Gaugaz, Pär Matsson, Per Artursson Journal of Pharmaceutical Sciences Volume 105, Issue 2, Pages 1017-1021 (February 2016) DOI: 10.1016/S0022-3549(15)00171-9 Copyright © 2016 Terms and Conditions

Figure 1 The CRISPR-Cas9 target region in exon 4 of the cAbcb1 gene. The cMdr1 KO Cl2 has a 4-nucleotide deletion compared to the wild-type gene; this leads to a frameshift missense mutation and premature stop codons downstream in exon 4. Journal of Pharmaceutical Sciences 2016 105, 1017-1021DOI: (10.1016/S0022-3549(15)00171-9) Copyright © 2016 Terms and Conditions

Figure 2 Transport of digoxin in the MDCK II wild-type (wt) cells and in the MDCK MDR1 knockout cells (cMdr1 KO Cl2). The cumulative fraction digoxin transported in the apical-to-basolateral direction and in the basolateral-to-apical direction in the wt (a) and in the cMdr1 KO Cl2 cells (b). Efflux ratios for digoxin alone and in the presence of the MDR1 inhibitor elacridar in the wt cells and the cMdr1 KO Cl2 cells (c). The dashed line indicates an efflux ratio of 1. Data are presented as mean ± standard deviation for 1 representative experiment performed in triplicate. ns, not significant. *p < 0.05. Journal of Pharmaceutical Sciences 2016 105, 1017-1021DOI: (10.1016/S0022-3549(15)00171-9) Copyright © 2016 Terms and Conditions

Figure 3 Efflux ratios for prototypic MDR1 substrates in the MDCK II wt and in the cMdr1 KO Cl2. The dashed line indicates an efflux ratio of 1. Data are presented as mean ± standard deviation for 1-3 experiments each performed in triplicate. ns, not significant. *p < 0.05; **p < 0.01; and ***p < 0.001. Journal of Pharmaceutical Sciences 2016 105, 1017-1021DOI: (10.1016/S0022-3549(15)00171-9) Copyright © 2016 Terms and Conditions