Mrp2 Knockout Rat
Model Detail >
- Efflux assays
- Drug-drug interactions
- Tissue distribution
- Dubin-Johnson syndrome
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Homozygous Mrp2 null rats display compromised biliary excretion and hyperbilirubinemia. This results in accumulation of glutathione-conjugated drugs in the liver.
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- Biallelic 726 bp deletion within Abcc2 gene
- Homozygous knockouts display total loss of protein via Western blot
- Decreased transport of endogenous glutathione
- Background Strain: Sprague-Dawley
Table 1. Glutathione level of Mrp2 (-/-) and wild type rats (nM/g)
Table 2. Serum chemistry for Mrp2 (-/-) and wild type rats
Mrp2 is expressed in the liver and functions in biliary transport. The gene’s substrates include anticancer compounds such as vinblastine, enabling it to confer multiple drug resistance to tumor cells. This model is useful for forumational, efficacy, tissue distribution, and DMPK assays.
- 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