Mdr1a Knockout Rat
Model Detail >
- DMPK Assay
- Efflux Assay
- Drug-drug interactions
- Drug resistance
- Blood brain barrier efflux
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P-glycoprotein plays a critical role in efflux for both brain and liver. Homozygous null Mdr1a rats display increased exposure to CNS drugs in the brain, as well as increased bioavailability in the plasma for P-gp-specific substrates.
- Biallelic 20 bp deletion within Abcba1 gene
- Increased oral bioavailability of P-gp-specific substrates
- Homozygous knockout rats display total loss of protein via Western blot
- Background Strain: Sprague-Dawley
Figure 1. Oral absorption of Digoxin in the absence and presence of Quinidine
Figure 2. Western blot using proximal colon tissue isolated from both wild type and Mdr1a homozygous knockout tissue
MDR1 encodes for P-glycoprotein and is a membrane-bound drug transporter expressed in the brain and intestine. It effectively blocks drugs from crossing the blood-brain barrier. P-gp can confer multiple drug resistance to tumor cells. Absence of P-gp creates a functional deficiency in the blood-brain barrier and results in elevated drug levels in many tissues, making this a useful model for efflux assay, efficacy, formulation, tissue distribution, studying neurotoxicology and chemotherapeutic agents.
- Zamek-Gliszczynski, M, et al. Minor compensatory changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats do not detract from their utility in the study of transporter-mediated pharmacokinetics.
- Zamek-Gliszczynski, M, et al. Characterization of SAGE Labs Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats using loperamide, paclitaxel, sulfasalazine, and carboxydichlorofluorescein pharmacokinetics. DMD. 2012
- Bundgaard, C. Species comparison of in vivo P-glycoprotein mediated brain efflux using mdr1a deficient rats and mice. DMD. 2012