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Strain Name
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C57BL/6N-Abcb1atm1Bcgen Abcb1btm1Bcgen/Bcgen
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Common Name
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B-Mdr1 KO mice
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Background
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C57BL/6N
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Catalog number
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112683
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Aliases
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CLCS; MDR1; P-GP; PGY1; ABC20; CD243; GP170; Abcb1a,Abcb1b
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Targeting strategy
Gene targeting strategy for B-Mdr1 KO mice. The genome sequences between mouse Mdr1a gene and Mdr1b gene were depleted in B-Mdr1 KO mice. As a result, mouse MDR1 protein will be not expressed anymore.
mRNA expression analysis
Mdr1a mRNA expression analysis in wild-type C57BL/6 mice and B-Mdr1 KO mice by RT-PCR. Brain, lung and liver RNA were isolated from wild-type C57BL/6 mice and B-Mdr1 KO mice, then cDNA libraries were synthesized by reverse transcription, followed by PCR with two mouse Mdr1a primer pairs. Mouse Mdr1a mRNA was not detectable in Mdr-1 knock-out mice.
Mdr1b mRNA expression analysis in wild-type C57BL/6 mice and B-Mdr1 KO mice by RT-PCR. Brain, lung and liver RNA were isolated from wild-type C57BL/6 mice and B-Mdr1 KO mice, then cDNA libraries were synthesized by reverse transcription, followed by PCR with two mouse Mdr1b primer pairs. Mouse Mdr1b mRNA was not detectable in Mdr-1 knock-out mice.
Protein expression analysis
Western blot analysis of MDR1 protein expression in B-Mdr1 KO mice. Various tissue lysates were collected from wild-type C57BL/6 mice and B-Mdr1 KO mice, and then analyzed by western blot with anti-MDR1A antibody. 40μg total proteins were loaded for western blotting analysis. MDR1 was only detectable in adrenal, brain, kidney and lung from wild-type mice but not in Mdr-1 knock-out mice.
Determination of plasma concentrations of Digoxin in B-Mdr1 KO mice
Pharmacokinetic characteristic of B-Mdr1 KO mice. Digoxin pharmacokinetics in C57BL/6N mice co-administered with vehicle or Elacridar and in B-Mdr1 KO mice. Mice received Digoxin (1 mg/kg, PO) as a single dose. For C57BL/6N groups, either vehicle or Elacridar (50 mg/kg, PO) was administered twice daily (BID) with an 8-hour interval, with the first dose given 0.5 hours prior to digoxin. B-Mdr1 KO mice received digoxin alone. Plasma samples were collected pre-dose and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours post digoxin administration (N=3 male mice per group). The plasma concentrations of digoxin in both the C57BL/6N with Elacridar group and B-Mdr1 KO mice group were higher than those in the C57BL/6N with Blank vehicle group.
Note: This experiment was conducted by Pharmaron using B-Mdr1 KO mice.
