Abcb1a

Summary

Gene Symbol: Abcb1a
Description: ATP-binding cassette, sub-family B (MDR/TAP), member 1A
Alias: Abcb4, Evi32, Mdr1a, Mdr3, P-gp, Pgp, Pgy-3, Pgy3, mdr-3, multidrug resistance protein 1A, ATP-binding cassette sub-family B member 1A, ATP-binding cassette, sub-family B (MDR/TAP), member 4, ATP-binding cassette, subfamily B, member 1A, P-glycoprotein 3, ecotropic viral integration site 32, multi-drug resistance 3, multidrug resistance protein 3, multiple drug resistant 1a
Species: mouse
Products:     Abcb1a

Top Publications

  1. Jonker J, Freeman J, Bolscher E, Musters S, Alvi A, Titley I, et al. Contribution of the ABC transporters Bcrp1 and Mdr1a/1b to the side population phenotype in mammary gland and bone marrow of mice. Stem Cells. 2005;23:1059-65 pubmed
    ..The ATP-binding cassette transporters Bcrp1 (Abcg2) and Mdr1a/1b (Abcb1a/1b) have been implicated as being responsible for this phenotype...
  2. 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
  3. Panwala C, Jones J, Viney J. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol. 1998;161:5733-44 pubmed
    The murine multiple drug resistance (mdr) gene, mdr1a, encodes a 170-kDa transmembrane protein that is expressed in many tissues including intestinal epithelial cells, a subset of lymphoid cells and hematopoietic cells...
  4. Soontornmalai A, Vlaming M, Fritschy J. Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier. Neuroscience. 2006;138:159-69 pubmed
    ..Analysis of Mdr1a(0/0) and Mrp1(0/0) mice, generated in the FVB strain, revealed no major alteration in expression of the remaining ..
  5. Croop J, Raymond M, Haber D, Devault A, Arceci R, Gros P, et al. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues. Mol Cell Biol. 1989;9:1346-50 pubmed
    ..5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in relation to understanding the normal physiological function of the mdr multigene family. ..
  6. Muller M, Keck M, Binder E, Kresse A, Hagemeyer T, Landgraf R, et al. ABCB1 (MDR1)-type P-glycoproteins at the blood-brain barrier modulate the activity of the hypothalamic-pituitary-adrenocortical system: implications for affective disorder. Neuropsychopharmacology. 2003;28:1991-9 pubmed
  7. Tsai C, Daood M, Lane R, Hansen T, Gruetzmacher E, Watchko J. P-glycoprotein expression in mouse brain increases with maturation. Biol Neonate. 2002;81:58-64 pubmed
    The mdr1a isoform of P-glycoprotein (Pgp) is an integral plasma membrane efflux pump expressed in adult brain capillary endothelial cells and astrocytes of the blood-brain barrier...
  8. Schinkel A, Smit J, van Tellingen O, Beijnen J, Wagenaar E, van Deemter L, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell. 1994;77:491-502 pubmed
    We have generated mice homozygous for a disruption of the mdr1a (also called mdr3) gene, encoding a drug-transporting P-glycoprotein...
  9. Schinkel -. P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev. 1999;36:179-194 pubmed
    ..The clinical application of P-glycoprotein blockers should also be considered in order to improve the blood-brain barrier permeability of certain drugs that currently display insufficient brain penetration for effective therapy. ..

More Information

Publications92

  1. Eisenbraun M, Miller R. mdr1a-encoded P-glycoprotein is not required for peripheral T cell proliferation, cytokine release, or cytotoxic effector function in mice. J Immunol. 1999;163:2621-7 pubmed
    ..Protein expression and rhodamine-123 efflux studies revealed that peripheral T cells exclusively utilize the mdr1a-encoded isoform rather than the homologous mdr1b or mdr2 isoforms...
  2. Uhr M, Holsboer F, Müller M. Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone and progesterone into the brain is enhanced in mice deficient for both mdr1a and mdr1b P-glycoproteins. J Neuroendocrinol. 2002;14:753-9 pubmed
    ..We used mice deficient for both murine mdr1a and mdr1b P-gps [mdr1a/1b(-/-)] to determine the uptake of [3H]-cortisol, [3H]-corticosterone, [3H]-aldosterone ..
  3. Johnson D, Finch R, Lin Z, Zeiss C, Sartorelli A. The pharmacological phenotype of combined multidrug-resistance mdr1a/1b- and mrp1-deficient mice. Cancer Res. 2001;61:1469-76 pubmed
    ..transporters to the toxicity of cancer chemotherapy agents, we have used mice genetically deficient in both the mdr1a and mdr1b genes [mdr1a/1b(-/-) mice], the mrp1 gene [mrp1(-/-) mice], and the combined genes mdr1a/1b and mrp1 [..
  4. Devault A, Gros P. Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities. Mol Cell Biol. 1990;10:1652-63 pubmed
    We report the cloning and functional analysis of a complete clone for the third member of the mouse mdr gene family, mdr3. Nucleotide and predicted amino acid sequence analyses showed that the three mouse mdr genes encode highly ..
  5. Schuetz E, Umbenhauer D, Yasuda K, Brimer C, Nguyen L, Relling M, et al. Altered expression of hepatic cytochromes P-450 in mice deficient in one or more mdr1 genes. Mol Pharmacol. 2000;57:188-97 pubmed
    ..We began with variants of a CF-1 mouse strain containing a defective mdr1a gene that is inherited in a Mendelian fashion...
  6. Schinkel A, Mayer U, Wagenaar E, Mol C, van Deemter L, Smit J, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci U S A. 1997;94:4028-33 pubmed
    ..roles, we have generated mice genetically deficient in the mdr1b gene [mdr1b (-/-) mice] and in both the mdr1a and mdr1b genes [mdr1a/1b (-/-) mice]...
  7. van Helvoort A, Smith A, Sprong H, Fritzsche I, Schinkel A, Borst P, et al. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell. 1996;87:507-17 pubmed
    The human MDR1 P-glycoprotein (Pgp) extrudes a variety of drugs across the plasma membrane. The homologous MDR3 Pgp is required for phosphatidylcholine secretion into bile...
  8. Schinkel A, Wagenaar E, Mol C, van Deemter L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest. 1996;97:2517-24 pubmed
    The mouse mdr1a (also called mdr3) P-GP is abundant in the blood-brain barrier, and its absence in mdr1a (-/-) mice leads to highly increased levels of the drugs ivermectin, vinblastine, digoxin, and cyclosporin A in the brain...
  9. Xu D, Regner M, Smith D, Ruby J, Johnstone R, Mullbacher A. The multidrug resistance gene mdr1a influences resistance to ectromelia virus infection by mechanisms other than conventional immunity. Immunol Cell Biol. 2004;82:462-70 pubmed
    ..We employed mdr1a gene knock out (mdr1a-/-) mice and ectromelia virus (EV) to elucidate the role of P-gp in resistance to EV...
  10. Schinkel A, Wagenaar E, van Deemter L, Mol C, Borst P. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest. 1995;96:1698-705 pubmed
    We have previously shown that absence of the mouse mdr1a (also called mdr3) P-glycoprotein in mdr1a (-/-) "knockout" mice has a profound effect on the tissue distribution and elimination of vinblastine and ivermectin, and hence ..
  11. Aller S, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009;323:1718-22 pubmed publisher
    ..The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding...
  12. Mason B, Pariante C, Thomas S. A revised role for P-glycoprotein in the brain distribution of dexamethasone, cortisol, and corticosterone in wild-type and ABCB1A/B-deficient mice. Endocrinology. 2008;149:5244-53 pubmed publisher
    ..Therefore, our current understanding of the role of P-gp in hypothalamic-pituitary-adrenal regulation in mice requires revision...
  13. Yang J, Milton M, Yu S, Liao M, Liu N, Wu J, et al. P-glycoprotein and breast cancer resistance protein affect disposition of tandutinib, a tyrosine kinase inhibitor. Drug Metab Lett. 2010;4:201-12 pubmed
    ..In mice, after intravenous administration of tandutinib, the mean plasma AUC values in the Bcrp1(-/-) mice and Mdr1a/b(-/-) mice was 1.53- and 1.20-fold greater than that of the wild type (WT) mice, respectively...
  14. Wijnholds J, deLange E, Scheffer G, van den Berg D, Mol C, van der Valk M, et al. Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J Clin Invest. 2000;105:279-85 pubmed
    ..Here, we generated Mrp1/Mdr1a/Mdr1b triple-knockout (TKO) mice, and used them together with Mdr1a/Mdr1b double-knockout (DKO) mice to study the ..
  15. Tombline G, Bartholomew L, Tyndall G, Gimi K, Urbatsch I, Senior A. Properties of P-glycoprotein with mutations in the "catalytic carboxylate" glutamate residues. J Biol Chem. 2004;279:46518-26 pubmed
    ..Here the role of these residues (Glu-552 and Glu-1197 in mouse MDR3 Pgp) was studied further. Mutation E552Q or E1197Q reduced Pgp-ATPase to low but still measurable rates...
  16. Krohn M, Lange C, Hofrichter J, Scheffler K, Stenzel J, Steffen J, et al. Cerebral amyloid-? proteostasis is regulated by the membrane transport protein ABCC1 in mice. J Clin Invest. 2011;121:3924-31 pubmed publisher
    ..Thus, by altering the temporal aggregation profile of A?, pharmacological activation of ABC transporters could impede the neurodegenerative cascade that culminates in the dementia of AD. ..
  17. Zhao Y, Du J, Kanazawa H, Cen X, Takagi K, Kitaichi K, et al. Shiga-like toxin II modifies brain distribution of a P-glycoprotein substrate, doxorubicin, and P-glycoprotein expression in mice. Brain Res. 2002;956:246-53 pubmed
    ..The present findings indicate that SLT-II impairs the BBB function and doxorubicin transport across the BBB, while it overexpresses P-glycoprotein. ..
  18. 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...
  19. 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. ..
  20. Schoenfelder Y, Hiemke C, Schmitt U. Behavioural consequences of p-glycoprotein deficiency in mice, with special focus on stress-related mechanisms. J Neuroendocrinol. 2012;24:809-17 pubmed publisher
    ..The P-gp knockout mouse model [abcb1a/b (-/-)] has been shown to differ in the functioning of the hypothalamic-pituitary adrenal (HPA) axis...
  21. Pan L, Aller S. Equilibrated atomic models of outward-facing P-glycoprotein and effect of ATP binding on structural dynamics. Sci Rep. 2015;5:7880 pubmed publisher
    P-glycoprotein (Pgp) is an ATP-binding cassette (ABC) transporter that alternates between inward- and outward-facing conformations to capture and force substrates out of cells like a peristaltic pump...
  22. Scialis R, Csanaky I, Goedken M, Manautou J. Multidrug Resistance-Associated Protein 3 Plays an Important Role in Protection against Acute Toxicity of Diclofenac. Drug Metab Dispos. 2015;43:944-50 pubmed publisher
    ..Overall, the data provide strong evidence that (1) in vivo Mrp3 plays an important role in DCF-AG disposition and (2) compromised Mrp3 function can enhance injury in the gastrointestinal tract after DCF treatment. ..
  23. Doricakova A, Theile D, Weiss J, Vrzal R. Differential effects of the enantiomers of tamsulosin and tolterodine on P-glycoprotein and cytochrome P450 3A4. Naunyn Schmiedebergs Arch Pharmacol. 2017;390:49-59 pubmed publisher
    ..The effect on CYP3A4 expression followed the same pattern but was much weaker. Taken together, tamsulosin and tolterodine are demonstrated to interfere with P-gp and CYP3A4 regulation in an enantiomer-specific way. ..
  24. Docolomansky P, Fialová I, Barancik M, Rybár A, Breier A. Prolongation of pentoxifylline aliphatic side chain positively affects the reversal of P-glycoprotein-mediated multidrug resistance in L1210/VCR line cells. Gen Physiol Biophys. 2005;24:461-6 pubmed
    ..We found that both PTX-UHM and PTX were able to reverse vincristine resistance of L1210/VCR cells, yet PTX-UHM was significantly more efficient in the reversal than PTX. ..
  25. Rawles L, Acuna D, Erickson R. The role of multiple drug resistance proteins in fetal and/or placental protection against teratogen-induced orofacial clefting. Mol Reprod Dev. 2007;74:1483-9 pubmed
    ..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,..
  26. Cohen D, Yu L, Rzepka R, Horwitz S. Identification of two nuclear protein binding sites and their role in the regulation of the murine multidrug resistance mdr1a promoter. DNA Cell Biol. 1994;13:641-9 pubmed
    ..In murine MDR cells, mdr1a and/or mdr1b genes are overexpressed and P-gp isoforms are overproduced...
  27. Ma L, Wei S, Yang B, Ma W, Wu X, Ji H, et al. Chrysosplenetin inhibits artemisinin efflux in P-gp-over-expressing Caco-2 cells and reverses P-gp/MDR1 mRNA up-regulated expression induced by artemisinin in mouse small intestine. Pharm Biol. 2017;55:374-380 pubmed
    ..These results confirm that CHR inhibited P-gp activity and reverse the up-regulated P-gp and MDR1 levels induced by ART. It suggested that CHR potentially can be used as a P-gp reversal agent to obstruct ART multidrug resistance. ..
  28. Erickson R, Kiela M, Garver W, Krishnan K, Heidenreich R. Cholesterol signaling at the endoplasmic reticulum occurs in npc1(-/-) but not in npc1(-/-), LDLR(-/-) mice. Biochem Biophys Res Commun. 2001;284:326-30 pubmed
    ..A large decrease in processed SREBP-1 was evident in fasted npc1(-/-) mice and npc1(-/-), mdr1a(-/-) mice, with no decrease evident in npc1(-/-), LDLR(-/-) mice...
  29. Bardelmeijer H, Beijnen J, Brouwer K, Rosing H, Nooijen W, Schellens J, et al. Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Clin Cancer Res. 2000;6:4416-21 pubmed
    Previous studies in mice with disrupted mdr1a P-glycoprotein genes have shown that the oral bioavailability of paclitaxel is very low because of the presence of this drug-transporting protein in the intestinal wall...
  30. Phoenix T, Patmore D, Boop S, Boulos N, Jacus M, Patel Y, et al. Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. Cancer Cell. 2016;29:508-522 pubmed publisher
    ..Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors. ..
  31. Patutina O, Mironova N, Popova N, Kaledin V, Nikolin V, Vlassov V, et al. The siRNA targeted to mdr1b and mdr1a mRNAs in vivo sensitizes murine lymphosarcoma to chemotherapy. BMC Cancer. 2010;10:204 pubmed publisher
    ..In this study, we used the siRNAs targeted to mdr1b, mdr1a, and bcl-2 mRNAs to reverse the MDR of tumors and increase tumor sensitivity to chemotherapeutics...
  32. 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
    ..the differential 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...
  33. Kirkinezos I, Hernandez D, Bradley W, Moraes C. An ALS mouse model with a permeable blood-brain barrier benefits from systemic cyclosporine A treatment. J Neurochem. 2004;88:821-6 pubmed
    ..blood-brain barrier, by crossing the G93A-SOD1 transgenic mouse with a multiple drug resistance type 1a/b (mdr1a/b) gene knockout mouse. To validate the model, we administered cyclosporine A intraperitoneally to the mice...
  34. Vlaming M, Teunissen S, van de Steeg E, van Esch A, Wagenaar E, Brunsveld L, et al. Bcrp1;Mdr1a/b;Mrp2 combination knockout mice: altered disposition of the dietary carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and its genotoxic metabolites. Mol Pharmacol. 2014;85:520-30 pubmed publisher
    ..To investigate the overlapping functions of Bcrp1, Mdr1a/b, and Mrp2 in vivo, we generated Bcrp1;Mdr1a/b;Mrp2(-/-) mice, which are viable and fertile...
  35. Jin M, Shimada T, Yokogawa K, Nomura M, Ishizaki J, Piao Y, et al. Site-dependent contributions of P-glycoprotein and CYP3A to cyclosporin A absorption, and effect of dexamethasone in small intestine of mice. Biochem Pharmacol. 2006;72:1042-50 pubmed
    ..method was used to evaluate the uptake of cyclosporin A (40nmol) at the upper and lower intestine of wild-type and mdr1a/1b knockout mice treated or not treated with dexamethasone (75mg/kg/day, 7 days, i.p.)...
  36. Kalabis G, Kostaki A, Andrews M, Petropoulos S, Gibb W, Matthews S. Multidrug resistance phosphoglycoprotein (ABCB1) in the mouse placenta: fetal protection. Biol Reprod. 2005;73:591-7 pubmed
    ..In the mouse, two genes, Abcb1a and Abcb1b, encode ABCB1...
  37. ErdÅ‘ F, Nagy I, Tóth B, Bui A, Molnár Ã, Tímár Z, et al. Abcb1a (P-glycoprotein) limits brain exposure of the anticancer drug candidate seliciclib in vivo in adult mice. Brain Res Bull. 2017;132:232-236 pubmed publisher
    ..that ABCB1/Abcb1 can limit brain exposure in vivo in mice we are showing that seliciclib is a substrate of mouse Abcb1a, the murine ABCB1 ortholog expressed in the BBB as LLC-PK-Abcb1a cells displayed an efflux ratio (ER) of 15...
  38. Zhang G, Zhang B, Fu X, Tomozawa H, Matsumoto K, Higuchi K, et al. Senescence-Accelerated Mouse (SAM) strains have a spontaneous mutation in the Abcb1a gene. Exp Anim. 2008;57:413-7 pubmed
    ..has a spontaneous retroviral insertional mutation in the ATP-binding cassette, sub-family B (MDR/TAP), member 1A (Abcb1a) gene...
  39. Jette L, Pouliot J, Murphy G, Beliveau R. Isoform I (mdr3) is the major form of P-glycoprotein expressed in mouse brain capillaries. Evidence for cross-reactivity of antibody C219 with an unrelated protein. Biochem J. 1995;305 ( Pt 3):761-6 pubmed
    ..Cross-reactivity of C219 with an unrelated protein emphasizes the fact that more than one antibody should be used in the assessment of P-gp expression in cell lines and tissues. ..
  40. Maxwell J, Zhang Y, Brown W, Smith C, Byrne F, Fiorino M, et al. Differential Roles for Interleukin-23 and Interleukin-17 in Intestinal Immunoregulation. Immunity. 2015;43:739-50 pubmed publisher
    ..This dichotomy between IL-23 and IL-17 was effectively modeled in the multidrug resistance-1a-ablated (Abcb1a(-/-)) mouse model of colitis...
  41. Kawahara M, Sakata A, Miyashita T, Tamai I, Tsuji A. Physiologically based pharmacokinetics of digoxin in mdr1a knockout mice. J Pharm Sci. 1999;88:1281-7 pubmed
    To determine the contribution of the mdr1a gene product to digoxin pharmacokinetics, we constructed a physiologically based pharmacokinetic model for digoxin in mdr1a (-/-) and mdr1a (+/+) mice...
  42. Petropoulos S, Gibb W, Matthews S. Developmental expression of multidrug resistance phosphoglycoprotein (P-gp) in the mouse fetal brain and glucocorticoid regulation. Brain Res. 2010;1357:9-18 pubmed publisher
    ..5-E15.5 (mid-gestation) or E12.5-E18.5 (late-gestation) and analyzed on E15.5 or E18.5. Abcb1a mRNA (P<0...
  43. Mason B, Thomas S, Lightman S, Pariante C. Desipramine treatment has minimal effects on the brain accumulation of glucocorticoids in P-gp-deficient and wild-type mice. Psychoneuroendocrinology. 2011;36:1351-60 pubmed publisher
    ..Overall, under the conditions tested, these results do not support the hypothesis that treatment with desipramine can inhibit P-gp at the BBB and subsequently increase the accumulation of glucocorticoids in the brain. ..
  44. Uhr M, Steckler T, Yassouridis A, Holsboer F. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology. 2000;22:380-7 pubmed
    Mice with a genetic disruption (knockout) of the multiple drug resistance (Mdr1a) gene were used to examine the effect of the absence of the drug-transporting P-glycoprotein at the blood-brain barrier on the uptake of amitriptyline (AMI) ..
  45. Spengler G, Molnar J, Viveiros M, Amaral L. Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein. Anticancer Res. 2011;31:4201-5 pubmed
  46. Boddupalli C, Nair S, Gray S, Nowyhed H, Verma R, Gibson J, et al. ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells. J Clin Invest. 2016;126:3905-3916 pubmed publisher
    ..These data identify a distinct subset of human T cells with a quiescent/slow-cycling phenotype, propensity for tissue enrichment, and potential to mobilize into circulation, which may be harnessed for adoptive cellular therapy. ..
  47. Murakami Y, Higashi Y, Matsunaga N, Koyanagi S, Ohdo S. Circadian clock-controlled intestinal expression of the multidrug-resistance gene mdr1a in mice. Gastroenterology. 2008;135:1636-1644.e3 pubmed publisher
    ..Although intestinal expression of the mdr1a gene and its efflux pump function has been shown to exhibit 24-hour variation, the mechanism of the variations ..
  48. Ey B, Eyking A, Klepak M, Salzman N, Gothert J, Runzi M, et al. Loss of TLR2 worsens spontaneous colitis in MDR1A deficiency through commensally induced pyroptosis. J Immunol. 2013;190:5676-88 pubmed publisher
    ..signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency...
  49. Carbery I, Ji D, Harrington A, Brown V, Weinstein E, Liaw L, et al. Targeted genome modification in mice using zinc-finger nucleases. Genetics. 2010;186:451-9 pubmed publisher
    ..Three individual genes, multidrug resistant 1a (Mdr1a), jagged 1 (Jag1), and notch homolog 3 (Notch3), were targeted in FVB/N and C57BL/6 mice...
  50. Wang Y, Li Y, Yang S, Yang L. An in silico approach for screening flavonoids as P-glycoprotein inhibitors based on a Bayesian-regularized neural network. J Comput Aided Mol Des. 2005;19:137-47 pubmed
    ..Our study indicates that the BRNN-based in silico model has good potential in facilitating the prediction of P-gp flavonoid inhibitors and might be applied in further drug design. ..
  51. Tam S, Richmond D, Kaminker J, Modrusan Z, Martin McNulty B, Cao T, et al. Death receptors DR6 and TROY regulate brain vascular development. Dev Cell. 2012;22:403-17 pubmed publisher
    ..These findings define a role for death receptors DR6 and TROY in CNS-specific vascular development. ..
  52. Pippert T, Umbenhauer D. The subpopulation of CF-1 mice deficient in P-glycoprotein contains a murine retroviral insertion in the mdr1a gene. J Biochem Mol Toxicol. 2001;15:83-9 pubmed
    ..This unusual sensitivity is the result of a deficiency in the mdr1a P-glycoprotein that normally contributes to a functional blood-brain barrier...
  53. 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
    ..These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs...
  54. Wen X, Gibson C, Yang I, Buckley B, Goedken M, Richardson J, et al. MDR1 transporter protects against paraquat-induced toxicity in human and mouse proximal tubule cells. Toxicol Sci. 2014;141:475-83 pubmed publisher
    ..proximal tubule epithelial cells (RPTEC) that endogenously express MDR1, HEK293 cells overexpressing MDR1, and Mdr1a/1b knockout mice...
  55. Dagenais C, Rousselle C, Pollack G, Scherrmann J. Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice. J Cereb Blood Flow Metab. 2000;20:381-6 pubmed
    ..of passive and carrier-mediated transport across the blood-brain barrier (BBB) was developed and applied to mdr1a P-glycoprotein (Pgp)-deficient mice [mdr1a(-/-)]. Cerebral flow was estimated from diazepam uptake...
  56. Jun K, Lee S, Shin H. Insertion of a retroviral solo long terminal repeat in mdr-3 locus disrupts mRNA splicing in mice. Mamm Genome. 2000;11:843-8 pubmed
  57. Murozono M, Matsumoto S, Okada S, Nagaoka D, Isshiki A, Watanabe Y. Reduction of brain infarction induced by a transient brain ischemia in mdr1a knockout mice. Neurochem Res. 2009;34:1555-61 pubmed publisher
    ..Neurosci Lett 24: 6-11, 2008). ..
  58. Mochida Y, Taguchi K, Taniguchi S, Tsuneyoshi M, Kuwano H, Tsuzuki T, et al. The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a suppresses polyp formation in Apc(Min/+) mice. Carcinogenesis. 2003;24:1219-24 pubmed
    ..We have introduced disrupted alleles of the murine P-gp gene, mdr1a, into Apc(Min/+) mice to evaluate whether P-gp plays any role in intestinal carcinogenesis...
  59. Carrier I, Gros P. Investigating the role of the invariant carboxylate residues E552 and E1197 in the catalytic activity of Abcb1a (mouse Mdr3). FEBS J. 2008;275:3312-24 pubmed publisher
    ..In Abcb1a, this invariant carboxylate residue corresponds to E552 in NBD1 and E1197 in NBD2...
  60. Zhang P, de Gooijer M, Buil L, Beijnen J, Li G, van Tellingen O. ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors. Int J Cancer. 2015;137:2007-18 pubmed publisher
    ..Although all tested EZH2 inhibitors are substrates of P-gp and BCRP, restricting the brain penetration and potential utility for treatment of glioma, EPZ-6438 would be the most suitable candidate of this series. ..
  61. Martinez L, Arnaud O, Hénin E, Tao H, Chaptal V, Doshi R, et al. Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein. FEBS J. 2014;281:673-82 pubmed publisher
    ..Crystal structure analysis suggests that the H site overlaps both QZ59-SSS locations while the R site overlaps the most embedded location. ..
  62. 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. To clarify the role of these three genes in the emergence of multidrug resistance and to initiate a structure-function ..
  63. Schumacher T, Krohn M, Hofrichter J, Lange C, Stenzel J, Steffen J, et al. ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice. PLoS ONE. 2012;7:e35613 pubmed publisher
    ..Therefore, we sought to determine brain-related phenotypic changes in animals lacking the expression of distinct ABC transporters (ABCB1, ABCG2 or ABCC1)...
  64. Kooij G, Backer R, Koning J, Reijerkerk A, van Horssen J, van der Pol S, et al. P-glycoprotein acts as an immunomodulator during neuroinflammation. PLoS ONE. 2009;4:e8212 pubmed publisher
    ..The function of the DC is severely impaired in P-gp knockout mice (Mdr1a/1b-/-), since both DC maturation and T cell stimulatory capacity is significantly decreased...
  65. Yokogawa K, Takahashi M, Tamai I, Konishi H, Nomura M, Moritani S, et al. P-glycoprotein-dependent disposition kinetics of tacrolimus: studies in mdr1a knockout mice. Pharm Res. 1999;16:1213-8 pubmed
    ..The blood and tissue concentrations of FK506 after i.v. or p.o. administration (2 mg/kg) to normal and mdr1a knockout mice were measured by competitive enzyme immunoassay...
  66. Banner K, Cattaneo C, Le Net J, Popovic A, Collins D, Gale J. Macroscopic, microscopic and biochemical characterisation of spontaneous colitis in a transgenic mouse, deficient in the multiple drug resistance 1a gene. Br J Pharmacol. 2004;143:590-8 pubmed
    ..that have been implicated in inflammatory bowel disease (IBD) (IL-8 and IFN-gamma) in the colon/rectum of mdr1a(-/-) mice, and by determining the sensitivity of these, together with the macroscopic, microscopic and disease ..
  67. Wang R, Chen H, Liu L, Sheps J, Phillips M, Ling V. Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump. Hepatology. 2009;50:948-56 pubmed publisher
    ..leads only to mild cholestasis with substantial bile flow and up-regulated P-glycoprotein genes (multidrug resistance protein 1a [Mdr1a] and Mdr1b)...
  68. Cisternino S, Mercier C, Bourasset F, Roux F, Scherrmann J. Expression, up-regulation, and transport activity of the multidrug-resistance protein Abcg2 at the mouse blood-brain barrier. Cancer Res. 2004;64:3296-301 pubmed
    ..prazosin and mitoxantrone, and the nonsubstrate vinblastine by the brains of wild-type and P-gp-deficient mutant mdr1a(-/-) mice with or without the P-gp/Abcg2 inhibitor GF120918 or the P-gp inhibitor PSC833...
  69. Huls M, Kramers C, Levtchenko E, Wilmer M, Dijkman H, Kluijtmans L, et al. P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury. Kidney Int. 2007;72:1233-41 pubmed
    ..In contrast, knockout mice had no signs of tubular damage. Our data indicate that P-gp knockout mice have impaired renal function but are protected against ischemic renal injury. ..
  70. Thevenod F, Hildebrandt J, Striessnig J, de Jonge H, Schulz I. Chloride and potassium conductances of mouse pancreatic zymogen granules are inversely regulated by a approximately 80-kDa mdr1a gene product. J Biol Chem. 1996;271:3300-5 pubmed
    ..of wild-type mice (+/+) or mice with a homozygous disruption of the multidrug resistance P-glycoprotein gene mdr1a (-/-)...
  71. Shaik N, Giri N, Pan G, Elmquist W. P-glycoprotein-mediated active efflux of the anti-HIV1 nucleoside abacavir limits cellular accumulation and brain distribution. Drug Metab Dispos. 2007;35:2076-85 pubmed
    ..In vivo brain distribution studies showed that the AUC(plasma) in mdr1a(-/-) CF-1 mutant mice was approximately 2-fold greater than the AUC(plasma) in the wild type, whereas the AUC(..
  72. Inui N, Hasegawa H, Suda T, Nakamura Y, Watanabe H, Chida K. Expression and function of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in lung dendritic cells from aging mice. J Gerontol A Biol Sci Med Sci. 2012;67:1049-55 pubmed publisher
    ..05). These data showed that LDCs from aged mice exhibited multidrug resistance protein 1- and multidrug resistance-associated protein 1-mediated efflux and that the age-associated changes differed according to transporters...
  73. Kranz J, Petzinger E, Geyer J. Brain penetration of the OAB drug trospium chloride is not increased in aged mice. World J Urol. 2013;31:219-24 pubmed publisher
  74. Erickson R, Kiela M, Devine P, Hoyer P, Heidenreich R. mdr1a deficiency corrects sterility in Niemann-Pick C1 protein deficient female mice. Mol Reprod Dev. 2002;62:167-73 pubmed
    ..We have introduced the mdr1a knockout into the npc1 mutant line...
  75. Lankas G, Cartwright M, Umbenhauer D. P-glycoprotein deficiency in a subpopulation of CF-1 mice enhances avermectin-induced neurotoxicity. Toxicol Appl Pharmacol. 1997;143:357-65 pubmed
  76. Ahn M, Ghaemmaghami S, Huang Y, Phuan P, May B, Giles K, et al. Pharmacokinetics of quinacrine efflux from mouse brain via the P-glycoprotein efflux transporter. PLoS ONE. 2012;7:e39112 pubmed publisher
    ..Our findings argue that the inhibition of the P-gp efflux transporter should improve the poor pharmacokinetic properties of quinacrine in the CNS. ..
  77. Henneman L, van Miltenburg M, Michalak E, Braumuller T, Jaspers J, Drenth A, et al. Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer. Proc Natl Acad Sci U S A. 2015;112:8409-14 pubmed publisher
    ..mouse carcinosarcomas resembling MBC show intrinsic resistance to olaparib caused by increased P-glycoprotein (Pgp) drug efflux transporter expression...
  78. Le Goff W, Settle M, Greene D, Morton R, Smith J. Reevaluation of the role of the multidrug-resistant P-glycoprotein in cellular cholesterol homeostasis. J Lipid Res. 2006;47:51-8 pubmed
  79. Pluchino K, Hall M, Moen J, Chufan E, Fetsch P, Shukla S, et al. Human-Mouse Chimeras with Normal Expression and Function Reveal That Major Domain Swapping Is Tolerated by P-Glycoprotein (ABCB1). Biochemistry. 2016;55:1010-23 pubmed publisher
    ..Overall, chimeras with one or two mouse P-gp domains were deemed functionally equivalent to human wild-type P-gp, demonstrating the ability of human P-gp to tolerate major structural changes. ..
  80. Dagenais C, Zong J, Ducharme J, Pollack G. Effect of mdr1a P-glycoprotein gene disruption, gender, and substrate concentration on brain uptake of selected compounds. Pharm Res. 2001;18:957-63 pubmed
    This study assessed the influence of mdr1a P-glycoprotein (P-gp) gene disruption, gender and concentration on initial brain uptake clearance (Clup) of morphine, quinidine and verapamil.
  81. Smit J, Huisman M, van Tellingen O, Wiltshire H, Schinkel A. Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest. 1999;104:1441-7 pubmed
    It was recently shown that naturally occurring Mdr1a mutant fetuses of the CF-1 outbred mouse stock have no placental Mdr1a P-glycoprotein (P-gp) and that this absence is associated with increased sensitivity to avermectin, a teratogenic ..
  82. Brückmann S, Brenn A, Grube M, Niedrig K, Holtfreter S, Von Bohlen Und Halbach O, et al. Lack of P-glycoprotein Results in Impairment of Removal of Beta-Amyloid and Increased Intraparenchymal Cerebral Amyloid Angiopathy after Active Immunization in a Transgenic Mouse Model of Alzheimer's Disease. Curr Alzheimer Res. 2017;14:656-667 pubmed publisher
    ..Our data indicate that the selective up-regulation of P-gp could enhance the efficacy of Aβ immunization in the treatment or prevention of AD. ..
  83. Bhushan A, Slapak C, Levy S, Tritton T. Expression of c-fos precedes MDR3 in vincristine and adriamycin selected multidrug resistant murine erythroleukemia cells. Biochem Biophys Res Commun. 1996;226:819-21 pubmed
    ..murine erythroleukemia sublines selected for resistance to vincristine or adriamycin which eventually overexpress mdr3. We speculate that early expression of c-fos prepares cells for overexpression of other genes, such as mdr3, that ..