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Gene Review

Abcc2  -  ATP-binding cassette, sub-family C...

Mus musculus

Synonyms: AI173996, ATP-binding cassette sub-family C member 2, Abc30, Canalicular multispecific organic anion transporter 1, Cmoat, ...
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Disease relevance of Abcc2

  • To obtain insight in the pharmacological and physiological functions of Mrp2, we generated Mrp2 knockout mice, which were viable and fertile but suffered from mild hyperbilirubinemia due to impaired excretion of bilirubin monoglucuronides into bile [1].
  • Therefore, we constructed first-generation recombinant adenoviruses encoding different shRNAs against murine ATP-binding cassette multidrug resistance protein 2 (Abcc2), which is involved in liver transport of bilirubin to bile, and analyzed Abcc2 silencing kinetics [2].
  • Moreover, Mrp2 (Abcc2) deficient animals display mild conjugated hyperbilirubinemia, corresponding to a human condition known as Dubin-Johnson syndrome (DJS) [3].
  • In the present study, we examined the role of charged amino acids in the transmembrane domains of rat Mrp2, conserved among MRP families, using the isolated membrane vesicles from Sf9 cells infected with the recombinant baculoviruses [4].

High impact information on Abcc2

  • No obvious changes were detected in the Mrp2, Mrp3, and Mrp4 mRNAs [5].
  • The transport activity found in the control NIH/3T3 cells may be ascribed to mouse cMOAT since Northern blot analysis indicated the presence of a transcript that hybridyzed to the carboxyl-terminal ATP-binding cassette sequence of the murine protein [6].
  • Although the membrane vesicles from the control NIH/3T3 cells exhibited endogenous activity in transporting DNP-SG and leukotriene C4 in an ATP-dependent manner, the transfection of cMOAT cDNA resulted in a significant increase in the transport activity for these ligands [6].
  • It is noteworthy that the most profound decrease in the biliary clearance of the glucuronide conjugates was observed in Bcrp-deficient mouse livers, although the biliary clearance of 4MUG was also approximately 35% lower in Mrp2-deficient mouse livers [7].
  • Multidrug resistance protein 2 is an important determinant of Paclitaxel pharmacokinetics [8].

Biological context of Abcc2


Anatomical context of Abcc2

  • CONCLUSION: These results indicate that OATP1B1 and OATP1B3 are at least partly responsible for the accumulation of TR-14035 into hepatocytes, and Mrp2 principally mediates the biliary excretion of TR-14035 [9].
  • Mrp2 cDNAs were isolated from BALB/c and Macaca fascicularis liver, respectively, and vesicle transport studies were performed using recombinant Mrp2s expressed in insect Sf9 cells [10].

Associations of Abcc2 with chemical compounds

  • Unlike in rats, where sulfate and glucuronide conjugates were excreted into bile predominantly by Mrp2, mouse Bcrp mediated the biliary excretion of sulfate metabolites and also played a major role in the biliary excretion of the glucuronide metabolites, with some minor contribution from mouse Mrp2 [7].
  • Their biliary excretion of doxorubicin after i.v. administration (5 mg/kg) was 54-fold decreased (0.32+/-0.13 versus 17.30+/-6.59 nmol/g liver in wild type), and a role for both Mdr1a/b and Mrp2 in this process was revealed [1].
  • After oral administration of the food-derived carcinogens [(14)C]PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and [14C]IQ (2-amino-3-methylimidazo[4,5-f]quinoline) plasma values were 1.9- and 1.7-fold higher in Mrp2-/- mice versus wild-type mice, respectively, demonstrating the role of Mrp2 in restricting exposure to these compounds [1].
  • C57/BL6 mice injected with these viruses showed significant impairment of Abcc2 function for up to 3 weeks, as reflected by increased serum bilirubin levels [2].
  • These results suggest that the biliary excretion of fexofenadine is mediated by unknown transporters distinct from P-gp, Mrp2, and Bcrp [11].

Other interactions of Abcc2

  • Subsequently, Mdr1a/b/Mrp2 knockout mice were generated [1].
  • Our results demonstrate that the Mrp2-/- mouse provides a valuable tool for studies of the impact of Mrp2 on behavior of drugs and other toxins, especially when combined with other ABC transporter knockout mice [1].
  • Hepatic Abcc3 protein levels, determined by immunoblot analysis, were approximately 60% higher in Abcc2-/- mice than in wild-type mice [12].
  • Recently, mice with gene disruptions in Mrp2, Mrp3 and Mrp4 have been developed [13].

Analytical, diagnostic and therapeutic context of Abcc2

  • After single-pass liver perfusion with 1 muM CDF diacetate for 30 min and an additional 30-min perfusion with CDF-free buffer, cumulative biliary excretion of CDF in Abcg2-/- mice was significantly higher than in wild-type mice (65 +/- 6 and 47 +/- 15% of dose, respectively, p < 0.05), whereas CDF recovery in bile of Abcc2-/- mice was negligible [12].


  1. Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2 (Abcc2) knockout mice. Vlaming, M.L., Mohrmann, K., Wagenaar, E., de Waart, D.R., Elferink, R.P., Lagas, J.S., van Tellingen, O., Vainchtein, L.D., Rosing, H., Beijnen, J.H., Schellens, J.H., Schinkel, A.H. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  2. Effect of Adenovirus-Mediated RNA Interference on Endogenous MicroRNAs in a Mouse Model of Multidrug Resistance Protein 2 Gene Silencing. Narvaiza, I., Aparicio, O., Vera, M., Razquin, N., Bortolanza, S., Prieto, J., Fortes, P. J. Virol. (2006) [Pubmed]
  3. Polymorphisms of MRP1 (ABCC1) and related ATP-dependent drug transporters. Conseil, G., Deeley, R.G., Cole, S.P. Pharmacogenet. Genomics (2005) [Pubmed]
  4. Charged amino acids in the transmembrane domains are involved in the determination of the substrate specificity of rat Mrp2. Ito, K., Suzuki, H., Sugiyama, Y. Mol. Pharmacol. (2001) [Pubmed]
  5. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. Kitada, H., Miyata, M., Nakamura, T., Tozawa, A., Honma, W., Shimada, M., Nagata, K., Sinal, C.J., Guo, G.L., Gonzalez, F.J., Yamazoe, Y. J. Biol. Chem. (2003) [Pubmed]
  6. Functional analysis of a canalicular multispecific organic anion transporter cloned from rat liver. Ito, K., Suzuki, H., Hirohashi, T., Kume, K., Shimizu, T., Sugiyama, Y. J. Biol. Chem. (1998) [Pubmed]
  7. The important role of bcrp (abcg2) in the biliary excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in mice. Zamek-Gliszczynski, M.J., Nezasa, K., Tian, X., Kalvass, J.C., Patel, N.J., Raub, T.J., Brouwer, K.L. Mol. Pharmacol. (2006) [Pubmed]
  8. Multidrug resistance protein 2 is an important determinant of Paclitaxel pharmacokinetics. Lagas, J.S., Vlaming, M.L., van Tellingen, O., Wagenaar, E., Jansen, R.S., Rosing, H., Beijnen, J.H., Schinkel, A.H. Clin. Cancer Res. (2006) [Pubmed]
  9. Characterization of Hepatobiliary Transport Systems of a Novel alpha4beta1/alpha4beta7 Dual Antagonist, TR-14035. Tsuda-Tsukimoto, M., Maeda, T., Iwanaga, T., Kume, T., Tamai, I. Pharm. Res. (2006) [Pubmed]
  10. Functional analysis of mouse and monkey multidrug resistance-associated protein 2 (mrp2). Ninomiya, M., Ito, K., Hiramatsu, R., Horie, T. Drug Metab. Dispos. (2006) [Pubmed]
  11. P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion. Tahara, H., Kusuhara, H., Fuse, E., Sugiyama, Y. Drug Metab. Dispos. (2005) [Pubmed]
  12. Altered hepatobiliary disposition of 5 (and 6)-carboxy-2',7'-dichlorofluorescein in Abcg2 (Bcrp1) and Abcc2 (Mrp2) knockout mice. Nezasa, K., Tian, X., Zamek-Gliszczynski, M.J., Patel, N.J., Raub, T.J., Brouwer, K.L. Drug Metab. Dispos. (2006) [Pubmed]
  13. Physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 as determined from recent studies on gene-disrupted mice. Kruh, G.D., Belinsky, M.G., Gallo, J.M., Lee, K. Cancer Metastasis Rev. (2007) [Pubmed]
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