Abcb4

Summary

Gene Symbol: Abcb4
Description: ATP-binding cassette, sub-family B (MDR/TAP), member 4
Alias: Mdr2, Pgy-2, Pgy2, mdr-2, phosphatidylcholine translocator ABCB4, ATP-binding cassette sub-family B member 4, P glycoprotein 2, P-glycoprotein 3, multidrug resistance protein 2, multidrug resistance protein 3
Species: mouse
Products:     Abcb4

Top Publications

  1. Katzenellenbogen M, Mizrahi L, Pappo O, Klopstock N, Olam D, Jacob Hirsch J, et al. Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice. Mol Cancer Res. 2007;5:1159-70 pubmed
    ..We investigated hepatocarcinogenesis in Mdr2-knockout (Mdr2-KO) mice, a model of inflammation-associated HCC, using gene expression profiling and ..
  2. Kirschner L. Amplification of the murine mdr2 gene and a reconsideration of the structure of the murine mdr gene locus. DNA Cell Biol. 1995;14:47-59 pubmed
    ..levels of amplification and expression for the mdr1b gene, but not for the other two gene family members, mdr1a and mdr2. To understand this phenomenon better, a study of the amplification and expression of the mdr2 gene was undertaken...
  3. Higgins C. P-glycoprotein. To flip or not to flip?. Curr Biol. 1994;4:259-60 pubmed
    The phenotype of mice homozygous for mutations of the mdr2 gene suggests that the mdr2 protein, which is closely related to the multidrug resistance P-glycoprotein, has a role in phospholipid transport.
  4. Chianale J, Vollrath V, Wielandt A, Miranda S, Gonzalez R, Fresno A, et al. Differences between nuclear run-off and mRNA levels for multidrug resistance gene expression in the cephalocaudal axis of the mouse intestine. Biochim Biophys Acta. 1995;1264:369-76 pubmed
    ..These results indicate that enterocytes of the ileum may be more actively involved in the P-glycoprotein-mediated transport of xenobiotics into the intestinal lumen. ..
  5. Mustacich D, Shields J, Horton R, Brown M, Reed D. Biliary secretion of alpha-tocopherol and the role of the mdr2 P-glycoprotein in rats and mice. Arch Biochem Biophys. 1998;350:183-92 pubmed
    ..Appl. Pharmacol. 139, 411-417 (1996)). The P-glycoprotein (Pgp) encoded by the mdr2 gene has been shown to transport phosphatidylcholine into the bile; therefore, in the current study, we utilized ..
  6. Klopstock N, Katzenellenbogen M, Pappo O, Sklair Levy M, Olam D, Mizrahi L, et al. HCV tumor promoting effect is dependent on host genetic background. PLoS ONE. 2009;4:e5025 pubmed publisher
    ..We crossed HCV-Tg mice that do not develop HCC with the Mdr2-knockout (Mdr2-KO) mice which develop inflammation-associated HCC, to generate Mdr2-KO/HCV-Tg mice...
  7. Mauad T, van Nieuwkerk C, Dingemans K, Smit J, Schinkel A, Notenboom R, et al. Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis. Am J Pathol. 1994;145:1237-45 pubmed
    The mouse mdr2 gene (and its human homologue MDR3, also called MDR2) encodes a P-glycoprotein that is present in high concentration in the bile canalicular membrane of hepatocytes...
  8. de Vree J, Ottenhoff R, Bosma P, Smith A, Aten J, Oude Elferink R. Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis. Gastroenterology. 2000;119:1720-30 pubmed
    ..Previous studies have shown that in the mdr2-knockout mouse, the animal model for this disease, the absence of phospholipids in bile causes chronic bile salt-..
  9. Fickert P, Fuchsbichler A, Wagner M, Zollner G, Kaser A, Tilg H, et al. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology. 2004;127:261-74 pubmed
    ..leading to bile duct damage in sclerosing cholangitis are unknown, we aimed to determine the pathogenesis of bile duct injury in multidrug resistance gene (Mdr2) (Abcb4) knockout mice (Mdr2(-/-)) as a novel model of the disease.

More Information

Publications90

  1. Pikarsky E, Porat R, Stein I, Abramovitch R, Amit S, Kasem S, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431:461-6 pubmed
    ..To test this hypothesis, we studied the Mdr2-knockout mouse strain, which spontaneously develops cholestatic hepatitis followed by hepatocellular carcinoma, a ..
  2. Katzenellenbogen M, Pappo O, Barash H, Klopstock N, Mizrahi L, Olam D, et al. Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice. Cancer Res. 2006;66:4001-10 pubmed
    Molecular events preceding the development of hepatocellular carcinoma were studied in the Mdr2-knockout (Mdr2-KO) mice...
  3. van Nieuwkerk C, Elferink R, Groen A, Ottenhoff R, Tytgat G, Dingemans K, et al. Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology. 1996;111:165-71 pubmed
    The mouse mdr2 gene encodes a P-glycoprotein expressed in the hepatocanalicular membrane. Inactivation of this gene causes lack of biliary phospholipid and cholesterol secretion and non-suppurative cholangitis...
  4. Katzenellenbogen M, Mizrahi L, Pappo O, Klopstock N, Olam D, Barash H, et al. Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice. Mol Cancer Ther. 2007;6:1283-91 pubmed
    ..We tested the effects of tannic acid and selenomethionine on hepatocellular carcinoma development in Mdr2 knockout (Mdr2-KO) mice...
  5. Smit J, Schinkel A, Oude Elferink R, Groen A, Wagenaar E, van Deemter L, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell. 1993;75:451-62 pubmed
    ..The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, ..
  6. Patsenker E, Popov Y, Stickel F, Jonczyk A, Goodman S, Schuppan D. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression. Gastroenterology. 2008;135:660-70 pubmed publisher
    ..Because its role in liver fibrosis is unknown, we studied alphavbeta6 function in vitro and explored the antifibrotic potential of the specific alphavbeta6 antagonist EMD527040...
  7. Nakken K, Nygard S, Haaland T, Berge K, Arnkvaern K, Ødegaard A, et al. Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers of Abcb4 (-/ - ) mice harbouring chronic cholangitis. Scand J Gastroenterol. 2007;42:1245-55 pubmed
    b>Abcb4 (-/-) mice secrete phosphatidylcholine-free, cytotoxic bile and develop chronic cholangitis...
  8. Raymond M, Rose E, Housman D, Gros P. Physical mapping, amplification, and overexpression of the mouse mdr gene family in multidrug-resistant cells. Mol Cell Biol. 1990;10:1642-51 pubmed
    The mouse mdr gene family consists of three distinct genes (mdr1, mdr2, and mdr3), for which we have isolated full-length cDNA clones...
  9. Lammert F, Wang D, Hillebrandt S, Geier A, Fickert P, Trauner M, et al. Spontaneous cholecysto- and hepatolithiasis in Mdr2-/- mice: a model for low phospholipid-associated cholelithiasis. Hepatology. 2004;39:117-28 pubmed
    ..Our aim now was to address whether spontaneous gallstone formation occurs in Mdr2 (Abcb4) knockout mice that are characterized by phospholipid-deficient bile...
  10. Buschman E, Arceci R, Croop J, Che M, Arias I, Housman D, et al. mdr2 encodes P-glycoprotein expressed in the bile canalicular membrane as determined by isoform-specific antibodies. J Biol Chem. 1992;267:18093-9 pubmed
    We have produced antibodies specific for the three P-glycoprotein (P-gp) isoforms encoded by the mouse mdr1, mdr2, and mdr3 genes...
  11. Gros P, Ben Neriah Y, Croop J, Housman D. Isolation and expression of a complementary DNA that confers multidrug resistance. Nature. 1986;323:728-31 pubmed
    ..Furthermore, because the cDNA was isolated from a drug-sensitive cell, mutations in the primary sequence of mdr are not required to produce a multidrug-resistance phenotype. ..
  12. Wettergren Y, Kullberg A, Levan G. Colcemid resistance in murine SEWA cells: non-Pgy gene amplification at low levels of resistance and preferential Pgy2 gene amplification at high levels of resistance. Hereditas. 1995;122:125-34 pubmed
    ..In contrast to actinomycin D-resistant SEWA cells, in which higher amplification levels of Pgy1 than of Pgy2 are regularly present, the COL-resistant lines showed a preference for Pgy2 gene amplification...
  13. Koopen N, Wolters H, Voshol P, Stieger B, Vonk R, Meier P, et al. Decreased Na+-dependent taurocholate uptake and low expression of the sinusoidal Na+-taurocholate cotransporting protein (Ntcp) in livers of mdr2 P-glycoprotein-deficient mice. J Hepatol. 1999;30:14-21 pubmed
    ..b>Mdr2 P-glycoprotein-deficient mice lack biliary phospholipids and cholesterol but show unchanged biliary bile salt ..
  14. Boudechiche L, Tranchart H, Branchereau S, Davit Spraul A, Laïnas P, Groyer Picard M, et al. Improvement of hepatocyte transplantation efficiency in the mdr2-/- mouse model by glyceryl trinitrate. Transplantation. 2015;99:36-40 pubmed publisher
    ..the effect of glyceryl trinitrate (GTN) on the efficacy of cell engraftment and on liver repopulation in the mdr2-knockout mouse, a model for progressive familial intrahepatic cholestasis type 3...
  15. Sokolovic A, Montenegro Miranda P, de Waart D, Cappai R, Duijst S, Sokolovic M, et al. Overexpression of insulin like growth factor binding protein 5 reduces liver fibrosis in chronic cholangiopathy. Biochim Biophys Acta. 2012;1822:996-1003 pubmed publisher
    The ATP-binding cassette, sub-family B member 4 knock-out mouse (Abcb4(-/-)) is a relevant model for chronic cholangiopathy in man...
  16. Li Z, Agellon L, Vance D. Choline redistribution during adaptation to choline deprivation. J Biol Chem. 2007;282:10283-9 pubmed
    ..Mice that lack both PEMT and MDR2 (multiple drug-resistant protein 2) successfully adapt to choline deprivation via hepatic choline recycling...
  17. Ruetz S, Gros P. Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell. 1994;77:1071-81 pubmed
    P-glycoproteins (P-gps) encoded by the mouse mdr2 and mdr3 genes were expressed in secretory vesicles (SVs) from the yeast mutant sec6-4, and their capacity to function as a lipid translocase/flippase was tested...
  18. Minich D, Voshol P, Havinga R, Stellaard F, Kuipers F, Vonk R, et al. Biliary phospholipid secretion is not required for intestinal absorption and plasma status of linoleic acid in mice. Biochim Biophys Acta. 1999;1441:14-22 pubmed
    ..We tested this hypothesis by investigating the intestinal absorption and the status of linoleic acid in mdr2 Pgp-deficient mice which secrete phospholipid-free bile...
  19. Hochrath K, Ehnert S, Ackert Bicknell C, Lau Y, Schmid A, Krawczyk M, et al. Modeling hepatic osteodystrophy in Abcb4 deficient mice. Bone. 2013;55:501-11 pubmed publisher
    ..the present study, we characterized the bone phenotypes of the ATP-binding cassette transporter B4 knockout mouse (Abcb4(-/-)), a well-established mouse model of chronic cholestatic liver disease, with the aim of identifying and ..
  20. Cai S, Mennone A, Soroka C, Boyer J. Altered expression and function of canalicular transporters during early development of cholestatic liver injury in Abcb4-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2014;306:G670-6 pubmed publisher
    Deficiency of ABCB4 is associated with several forms of cholestasis in humans. Abcb4(-/-) mice also develop cholestasis, but it remains uncertain what role other canalicular transporters play in the development of this disease...
  21. Sawicki W, Kujawa M, Jankowska Steifer E, Mystkowska E, Hyc A, Kowalewski C. Temporal/spatial expression and efflux activity of ABC transporter, P-glycoprotein/Abcb1 isoforms and Bcrp/Abcg2 during early murine development. Gene Expr Patterns. 2006;6:738-46 pubmed
    ..Between 7 and 8 dpc, at the onset of organogenesis, the vehement surge of efflux-inactive embryonic cells occurred, and their number increased in 9 dpc embryos, which consequently contained few efflux-active cells...
  22. Kunne C, de Graaff M, Duijst S, de Waart D, Oude Elferink R, Paulusma C. Hepatic cytochrome P450 deficiency in mouse models for intrahepatic cholestasis predispose to bile salt-induced cholestasis. Lab Invest. 2014;94:1103-13 pubmed publisher
    ..cholestasis (PFIC) types 1 and 3 are severe cholestatic liver diseases caused by deficiency of ATB8B1 and ABCB4, respectively...
  23. Groen A, van Wijland M, Frederiks W, Smit J, Schinkel A, Oude Elferink R. Regulation of protein secretion into bile: studies in mice with a disrupted mdr2 p-glycoprotein gene. Gastroenterology. 1995;109:1997-2006 pubmed
    ..and biliary lipid output were studied in wild-type mice (+/+), heterozygotes (+/-), and homozygotes (-/-) for mdr2 gene disruption...
  24. Kotaka M, Onishi Y, Ohno T, Akaike T, Ishida N. Identification of negative transcriptional factor E4BP4-binding site in the mouse circadian-regulated gene Mdr2. Neurosci Res. 2008;60:307-13 pubmed publisher
    The hepatic transporter Mdr2 is an ATP-binding cassette transporter which excretes phosphatidylcholine into the bile...
  25. Fickert P, Wagner M, Marschall H, Fuchsbichler A, Zollner G, Tsybrovskyy O, et al. 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology. 2006;130:465-81 pubmed
    ..Current therapy for primary sclerosing cholangitis is of limited efficacy. Multidrug resistance gene 2 knockout mice (Mdr2(-/-)) represent a well-characterized model for sclerosing cholangitis...
  26. Langheim S, Yu L, von Bergmann K, Lutjohann D, Xu F, Hobbs H, et al. ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile. J Lipid Res. 2005;46:1732-8 pubmed
    ..Three members of the ATP binding cassette (ABC) family, ABCG5 (G5), ABCG8 (G8), and ABCB4 (MDR2), are required for the efficient biliary export of sterols...
  27. Kok T, Bloks V, Wolters H, Havinga R, Jansen P, Staels B, et al. Peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in mice. Biochem J. 2003;369:539-47 pubmed
    ..Fibrates induce the hepatic expression of murine multidrug resistance 2 ( Mdr2 ), encoding the canalicular phospholipid translocator...
  28. Voshol P, Havinga R, Wolters H, Ottenhoff R, Princen H, Oude Elferink R, et al. Reduced plasma cholesterol and increased fecal sterol loss in multidrug resistance gene 2 P-glycoprotein-deficient mice. Gastroenterology. 1998;114:1024-34 pubmed
    b>mdr2 P-glycoprotein (Pgp) deficiency in mice leads to the absence of biliary phospholipids and cholesterol in the presence of normal bile salt secretion...
  29. Borst P, Schinkel A. What have we learnt thus far from mice with disrupted P-glycoprotein genes?. Eur J Cancer. 1996;32A:985-90 pubmed
  30. Voshol P, Minich D, Havinga R, Elferink R, Verkade H, Groen A, et al. Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice. Gastroenterology. 2000;118:173-82 pubmed
    ..phospholipids in dietary fat absorption in vivo by using mice homozygous or heterozygous for disruption of the Mdr2 gene (Mdr2((-/-)), Mdr2((+/-))) and control (Mdr2((+/+))) mice...
  31. Chianale J, Vollrath V, Wielandt A, Amigo L, Rigotti A, Nervi F, et al. Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse. Biochem J. 1996;314 ( Pt 3):781-6 pubmed
    Disruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids...
  32. Raymond M, Gros P. Cell-specific activity of cis-acting regulatory elements in the promoter of the mouse multidrug resistance gene mdr1. Mol Cell Biol. 1990;10:6036-40 pubmed
    ..The addition to the basal promoter of sequences upstream of position -141 was found to up or down regulate the basal level of expression of the reporter gene in a cell-specific manner. ..
  33. Singer S, Zhao R, Barsotti A, Ouwehand A, Fazollahi M, Coutavas E, et al. Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes. Mol Cell. 2012;48:799-810 pubmed publisher
    ..Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins. ..
  34. De Ponti A, Wiechert L, Stojanovic A, Longerich T, Marhenke S, Hogg N, et al. Chronic liver inflammation and hepatocellular carcinogenesis are independent of S100A9. Int J Cancer. 2015;136:2458-63 pubmed publisher
    ..Mice lacking S100a9 were crossed with the Mdr2(-/-) model, a prototype of inflammation-induced HCC formation...
  35. Werner A, Havinga R, Perton F, Kuipers F, Verkade H. Lymphatic chylomicron size is inversely related to biliary phospholipid secretion in mice. Am J Physiol Gastrointest Liver Physiol. 2006;290:G1177-85 pubmed
    ..Biliary PL secretion is absent in multidrug resistance protein 2-deficient (Mdr2(-/-)) mice, whereas it is strongly increased in essential fatty acid (EFA)-deficient ..
  36. Li Z, Agellon L, Vance D. The role of phosphatidylethanolamine methyltransferase in a mouse model of intrahepatic cholestasis. Biochim Biophys Acta. 2011;1811:278-83 pubmed publisher
    ..liver damage in intrahepatic cholestasis based on a mouse model that lacks multiple drug resistant protein 2 (ABCB4)...
  37. Frijters C, Tuijn C, Ottenhoff R, Zegers B, Groen A, Elferink R. The role of different P-glycoproteins in hepatobiliary secretion of fluorescently labeled short-chain phospholipids. J Lipid Res. 1999;40:1950-8 pubmed
    ..biliary secretion of C6-7-nitro-2,1, 3-benzoxadiazol-4-yl (NBD)-labeled ceramide and its metabolites in Mdr1a/b and Mdr2 knockout mice compared to control mice. Biliary secretion of these NBD-lipids was unaffected in Mdr1a/b -/- mice...
  38. Latasa M, Gil Puig C, Fernández Barrena M, Rodriguez Ortigosa C, Banales J, Urtasun R, et al. Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2-/- mice. PLoS ONE. 2010;5:e15690 pubmed publisher
    ..evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA) in Mdr2(-/-) mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at ..
  39. Tebbi A, Levillayer F, Jouvion G, Fiette L, Soubigou G, Varet H, et al. Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress. Carcinogenesis. 2016;37:39-48 pubmed publisher
    Multidrug resistance 2 (Mdr2), also called adenosine triphosphate-binding cassette B4 (ABCB4), is the transporter of phosphatidylcholine (PC) at the canalicular membrane of mouse hepatocytes, which plays an essential role for bile ..
  40. Kirschner L. De novo generation of simple sequence during gene amplification. Nucleic Acids Res. 1996;24:2829-34 pubmed
    ..V2-1 has been shown previously to contain two distinct forms of the highly amplified mdr2 gene, a member of the mouse gene family responsible for the multidrug resistant (MDR) phenotype [Kirschner, L. S...
  41. Hsu S, Lothstein L, Horwitz S. Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes. J Biol Chem. 1989;264:12053-62 pubmed
    ..amplification and/or transcriptional activation of three distinct but closely related mdr genes (mdr1a, mdr1b, and mdr2) in independently selected multidrug-resistant J774.2 mouse cell lines...
  42. Igolnikov A, Green R. Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet. J Hepatol. 2006;44:586-92 pubmed
    ..The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less ..
  43. Li Z, Agellon L, Vance D. Phosphatidylcholine homeostasis and liver failure. J Biol Chem. 2005;280:37798-802 pubmed
    ..PC secretion into bile is mediated by a PC-specific flippase, multiple drug-resistant protein 2 (MDR2). Here, we report that mice that lack both PEMT and MDR2 and are fed a CD diet survive for >90 days...
  44. Mederacke I, Hsu C, Troeger J, Huebener P, Mu X, Dapito D, et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun. 2013;4:2823 pubmed publisher
    ..On the basis these findings, HSCs should be considered the primary cellular target for antifibrotic therapies across all types of liver disease. ..
  45. Hefetz Sela S, Stein I, Klieger Y, Porat R, Sade Feldman M, Zreik F, et al. Acquisition of an immunosuppressive protumorigenic macrophage phenotype depending on c-Jun phosphorylation. Proc Natl Acad Sci U S A. 2014;111:17582-7 pubmed publisher
    ..Our findings identify c-Jun phosphorylation as a key mediator of macrophage education and point to the recruitment of immunosuppressive regulatory T cells as a possible protumorigenic mechanism. ..
  46. Werner A, Minich D, Havinga R, Bloks V, van Goor H, Kuipers F, et al. Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation. Am J Physiol Gastrointest Liver Physiol. 2002;283:G900-8 pubmed
    ..Identical dietary experiments were performed in multidrug resistance gene-2-deficient [Mdr2((-/-))] mice, secreting phospholipid-free bile...
  47. Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, et al. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 2002;31:320-5 pubmed
    ..to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury...
  48. Higashiyama H, Ozawa A, Sumitomo H, Uemura M, Fujino K, Igarashi H, et al. Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia. Development. 2017;144:1906-1917 pubmed publisher
  49. Dhir R, Buschman E, Gros P. Structural and functional characterization of the mouse multidrug resistance gene family. Bull Cancer. 1990;77:1125-9 pubmed
    The mouse multidrug resistance (mdr) gene family is composed of three closely related genes mdr1, mdr2 and mdr3...
  50. Ehlken H, Kondylis V, Heinrichsdorff J, Ochoa Callejero L, Roskams T, Pasparakis M. Hepatocyte IKK2 protects Mdr2-/- mice from chronic liver failure. PLoS ONE. 2011;6:e25942 pubmed publisher
    Mice lacking the Abc4 protein encoded by the multidrug resistance-2 gene (Mdr2(-/-)) develop chronic periductular inflammation and cholestatic liver disease resulting in the development of hepatocellular carcinoma (HCC)...
  51. Groen A, Romero M, Kunne C, Hoosdally S, Dixon P, Wooding C, et al. Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity. Gastroenterology. 2011;141:1927-37.e1-4 pubmed publisher
    Progressive familial intrahepatic cholestasis can be caused by mutations in ABCB4 or ATP8B1; each encodes a protein that translocates phospholipids, but in opposite directions...
  52. Gros P, Croop J, Housman D. Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell. 1986;47:371-80 pubmed
    ..We propose that an energy-dependent transport mechanism is responsible for the multidrug-resistant phenotype. ..
  53. Buschman E, Gros P. The inability of the mouse mdr2 gene to confer multidrug resistance is linked to reduced drug binding to the protein. Cancer Res. 1994;54:4892-8 pubmed
    The mouse mdr gene family is composed of three members designated mdr1, mdr2, and mdr3...
  54. Kruit J, Plosch T, Havinga R, Boverhof R, Groot P, Groen A, et al. Increased fecal neutral sterol loss upon liver X receptor activation is independent of biliary sterol secretion in mice. Gastroenterology. 2005;128:147-56 pubmed
    ..Various steps of this pathway are controlled by the liver X receptor (LXR). We addressed the role of the intestine in LXR-dependent stimulation of fecal cholesterol excretion...
  55. Philips G, Chan I, Swiderska M, Schroder V, Guy C, Karaca G, et al. Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer. PLoS ONE. 2011;6:e23943 pubmed publisher
    ..Mice with targeted deletion of Mdr2 (the murine ortholog of MDR3) develop chronic fibrosing liver injury...
  56. Oude Elferink R, Ottenhoff R, van Wijland M, Frijters C, Van Nieuwkerk C, Groen A. Uncoupling of biliary phospholipid and cholesterol secretion in mice with reduced expression of mdr2 P-glycoprotein. J Lipid Res. 1996;37:1065-75 pubmed
    Mice in which the gene for mdr2 P-glycoprotein has been disrupted have a severe deficiency in biliary phospholipid and cholesterol secretion...
  57. Shukla R, Upton K, Muñoz Lopez M, Gerhardt D, Fisher M, Nguyen T, et al. Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell. 2013;153:101-11 pubmed publisher
    ..ST18 was also frequently amplified in HCC nodules from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene...
  58. Ikenaga N, Liu S, Sverdlov D, Yoshida S, Nasser I, Ke Q, et al. A new Mdr2(-/-) mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer. Am J Pathol. 2015;185:325-34 pubmed publisher
    We previously characterized the Mdr2(Abcb4)(-/-) mouse as a reproducible model of chronic biliary liver disease. However, it demonstrates relatively slow fibrosis progression, possibly due to its fibrosis-resistant genetic background...
  59. Sancho P, Mainez J, Crosas Molist E, Roncero C, Fernandez Rodriguez C, Pinedo F, et al. NADPH oxidase NOX4 mediates stellate cell activation and hepatocyte cell death during liver fibrosis development. PLoS ONE. 2012;7:e45285 pubmed publisher
    ..Two different mice models that develop spontaneous fibrosis (Mdr2(-/-)/p19(ARF-/-), Stat3(?hc)/Mdr2(-/-)) and a model of experimental induced fibrosis (CCl(4)) were used...
  60. Li Z, Agellon L, Allen T, Umeda M, Jewell L, Mason A, et al. The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab. 2006;3:321-31 pubmed
    ..Steatosis is observed in CD mice that lack both PEMT and multiple drug-resistant protein 2 (MDR2), required for PC secretion into bile...
  61. Buschman E, Gros P. Functional analysis of chimeric genes obtained by exchanging homologous domains of the mouse mdr1 and mdr2 genes. Mol Cell Biol. 1991;11:595-603 pubmed
    ..In the same assay, a full-length cDNA clone for a closely related member of the mouse mdr gene family, mdr2, fails to confer multidrug resistance...
  62. Tabibian J, Macura S, O Hara S, Fidler J, Glockner J, Takahashi N, et al. Micro-computed tomography and nuclear magnetic resonance imaging for noninvasive, live-mouse cholangiography. Lab Invest. 2013;93:733-43 pubmed publisher
    ..Using mdr2 knockout (mdr2KO, a model for primary sclerosing cholangitis (PSC)), bile duct-ligated (BDL), and normal mice, we ..
  63. Smith A, Oude Elferink R. Liver gene disruptions: winners by KO?. J Hepatol. 1999;31:752-9 pubmed
  64. Bridle K, Sobbe A, de Guzman C, Santrampurwala N, Jaskowski L, Clouston A, et al. Lack of efficacy of mTOR inhibitors and ACE pathway inhibitors as antifibrotic agents in evolving and established fibrosis in Mdr2?/? mice. Liver Int. 2015;35:1451-63 pubmed publisher
    ..of rapamycin, everolimus, irbesartan and captopril, alone and in combination, as antifibrotic agents in the Mdr2(-/-) model of cholestasis both in early injury and established disease...
  65. Barash H, R Gross E, Edrei Y, Ella E, Israel A, Cohen I, et al. Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks. Proc Natl Acad Sci U S A. 2010;107:2207-12 pubmed publisher
    ..b>Mdr2-KO mice, a model of inflammation-associated cancer, underwent partial hepatectomy (PHx), which led to enhanced ..
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    ..effects of bile duct proliferation under non-cholestatic conditions in multidrug resistance-2 P-glycoprotein (Abcb4)-deficient multidrug resistance gene-2 (Mdr2(-/-)) mice...
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    ..revealed that peripheral T cells exclusively utilize the mdr1a-encoded isoform rather than the homologous mdr1b or mdr2 isoforms...
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    Mice homozygous for a disruption in the Mdr2 gene (Mdr2 (-/-) mice) lack the Mdr2 P-glycoprotein (P-gp) in the canalicular membrane of the hepatocyte and are unable to excrete phosphatidylcholine into the bile...
  71. Kok T, Wolters H, Bloks V, Havinga R, Jansen P, Staels B, et al. Induction of hepatic ABC transporter expression is part of the PPARalpha-mediated fasting response in the mouse. Gastroenterology. 2003;124:160-71 pubmed
    ..e., fibrates, induce the hepatic expression of the multidrug resistance 2 gene (Mdr2), encoding the canalicular phospholipid translocator, and affect hepatobiliary lipid transport...
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    ..There are three mdr genes (mdr1, mdr2, and mdr3) in the mouse genome and two (MDR1 and MDR2) in the human genome; however, only two mouse genes (mdr1 and ..
  73. Tang Y, Beuerlein G, Pecht G, Chilton T, Huse W, Watkins J. Use of a peptide mimotope to guide the humanization of MRK-16, an anti-P-glycoprotein monoclonal antibody. J Biol Chem. 1999;274:27371-8 pubmed
    ..Thus, peptide mimotopes which can be identified for virtually any antibody including those that recognize conformational or carbohydrate epitopes, can serve as antigen templates for antibody engineering. ..
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    ..Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the ..
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    ..We have expanded the number of proteins and teratogens examined by comparing the influence of the mdr1a and mdr2 proteins on teratogen-induced orofacial clefting using their respective knockouts in crosses with the A/J, high ..
  76. Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae S, Ising M, et al. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008;57:203-9 pubmed publisher
    ..This finding can be viewed as a further step into personalized antidepressant treatment...
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    ..We investigated the consequences of fasting on liver fibrosis in Abcb4(-/-) mice that spontaneously develop it due to a lack of phospholipids in bile...
  78. Raymond M, Gros P. Mammalian multidrug-resistance gene: correlation of exon organization with structural domains and duplication of an ancestral gene. Proc Natl Acad Sci U S A. 1989;86:6488-92 pubmed
    ..The conservation of certain pairs of introns, together with the high degree of sequence homology, indicate that the mouse mdr1 gene originated from the duplication of an intron-containing ancestral gene. ..
  79. Jörs S, Jeliazkova P, Ringelhan M, Thalhammer J, Dürl S, Ferrer J, et al. Lineage fate of ductular reactions in liver injury and carcinogenesis. J Clin Invest. 2015;125:2445-57 pubmed publisher
    ..In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs. ..
  80. Strack I, Schulte S, Varnholt H, Schievenbusch S, Töx U, Wendland K, et al. ?-Adrenoceptor blockade in sclerosing cholangitis of Mdr2 knockout mice: antifibrotic effects in a model of nonsinusoidal fibrosis. Lab Invest. 2011;91:252-61 pubmed publisher
    ..cholangitis after inhibition of the sympathetic nervous system by blockade of the ?-adrenoceptors, we used the Mdr2(-/-) mouse model, which develops periportal fibrosis similar to human PSC...
  81. Hochrath K, Krawczyk M, Goebel R, Langhirt M, Rathkolb B, Micklich K, et al. The hepatic phosphatidylcholine transporter ABCB4 as modulator of glucose homeostasis. FASEB J. 2012;26:5081-91 pubmed publisher
    ..receptor-dependent PC pathway has been determined to exert antidiabetic effects, we now analyzed the role of ABCB4 in glucose metabolism...