Mdr1a/1b knockout rat

Mdr1a/1b knockout rat

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Rat model with knockout MDR1a i MDR 1b encodes P-glycoprotein. Used in clinical pharmacokinetics, pharmacodynamics, efficacy, neurotoxicology, multidrug resistance, efflox.

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  • Description
  • Publications

Mdr1a/1b knockout rat

Nomenclature: SD- Abcb1a-Abc1b tm1sage 

Genotype: Homozygous

Description: 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.

Research applications

  • DMPK assay
  • PK/PD
  • efflux assay
  • neurotoxicology
  • formulation
  • drug-drug interactions
  • drug resistance
  • blood brain barrier efflux
  • efficacy

Characteristics:

  • background strain: Sprague-Dawley

Coat color: White, albino.

Strain code: TGRS7070

Bred in: US

Additional information: 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.

Minor Compensatory Changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 Knockout Rats do not Detract from their General Utility in the Study of Transporter-mediated Pharmacokinetics

Maciej J Zamek-Gliszczynski, Keith M Goldstein, April Paulman, Thomas K Baker, Timothy P Ryan
DMD April 8, 2013 dmd.113.051409


Characterization of SAGE Mdr1a (P-gp), Bcrp, and Mrp2 Knockout Rats Using Loperamide, Paclitaxel, Sulfasalazine, and Carboxydichlorofluorescein Pharmacokinetics

Maciej J. Zamek-Gliszczynski, David W. Bedwell, Jing Q. Bao and J. William Higgins
DMD September 2012 vol. 40 no. 9 1825-1833


Species Comparison of In Vivo P-Glycoprotein-Mediated Brain Efflux Using mdr1a-Deficient Rats and Mice

Christoffer Bundgaard, Christian Jes Nyberg Jensen and Mats Garmer
DMD March 2012 vol. 40 no. 3 461-466


Brain Penetration of WEB 2086 (Apafant) and Dantrolene in Mdr1a (P-gp) and Bcrp Knockout Rats

Holger Fuchs, Wataru Kishimoto, Dietmar Gansser, Paul Tanswell, Naoki Ishiguro4
DMD July 22, 2014 dmd.114.058545