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Mdr1a-Bcrp knockout rat

LOCATIONS

Characteristics / Husbandry

  • Background strain: Sprague Dawley
  • Biallelic 20 bp deletion within Abcba1 gene and 588 bp deletion within the Abcg2 gene
  • Homozygous knockouts exhibit complete loss of ApoE protein via Western blot
  • Increased oral bioavailability of P-gp and Bcrp specific substrates

Availability: Live colony
Zygosity genotype: Homozygous

P-gp and Bcrp both play a critical role in efflux for brain. Double homozygous null Mdr1a-Bcrp rats display increased exposure to CNS drugs in the brain, as well as increased bioavailability in the plasma for P-gp and Bcrp specific substrates.

MDR1 and BCRP are membrane-bound drug transporters expressed in the brain. Each effectively blocks specific drugs from crossing the blood-brain barrier. P-gp and Bcrp can confer multiple drug resistance to tumor cells. Absence of P-gp and Bcrp 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.

Research Use & Related Publications
DMPK assay
PK-PD efflux assay
Neurotoxicology
Formulation drug-drug interactions
Drug resistance
Blood brain barrier efflux
Efficacy
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The Mdr1a - Bcrp KO rat model was originally created at SAGE Labs, Inc. in St. Louis, MO and distributed out of the Boyertown, PA facility. The line continues to be maintained through the original SAGE Labs animal inventory acquired by Envigo.