FVB-Abcb1a&Abcb1b DKO (Mdr1a/b KO) Mice

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Product Number：C001493

Genetic Background：FVB

Reproduction：Homozygote x Homozygote


Strain Description

P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is an ATP-binding cassette transporter that acts as a biological barrier by expelling toxins and foreign substances from cells. P-gp is capable of transporting many structurally and functionally different compounds out of cells [1]. However, the mechanism of MDR1 also prevents the uptake of many cancer treatment drugs by cells, leading to multidrug resistance (MDR) [2]. In normal organisms, MDR1’s distribution in the blood-brain barrier and blood-placenta barrier prevents exogenous drugs and toxins from entering the central nervous system and placenta of the organism, thereby protecting the organism and enabling it to perform normal physiological functions. In pathological conditions, however, the MDR1 in the blood-brain barrier prevents drugs from entering the central nervous system, and in tumor cells, leads to the development of MDR. The evolution of MDR remains one of the major obstacles to controlling or curing cancer [3-4].

In humans, the MDR1 protein is encoded by the ABCB1 gene. In mice, two closely located genes, Abcb1a and Abcb1b, encode the MDR1a and MDR1b subtypes of this protein. Mouse MDR1a and MDR1b have 80% homology with human MDR1. MDR1a and MDR1b have the same function as human MDR1 protein in resisting anticancer drugs. Although mouse MDR1a and MDR1b proteins are distributed in different tissues of the body, their overall distribution is consistent with that of human MDR1 protein [5-6]. In summary, the distribution and function of mouse MDR1a and MDR1b are consistent with those of human MDR1.

This strain is an MDR1 knockout model, in which the human ABCB1 gene’s homologous genes, Abcb1a and Abcb1b, were knocked out in mice using gene editing technology. This model lacks the expression of MDR1 protein and can be used for research in areas such as blood-brain barrier permeability-related diseases and multidrug resistance of anti-tumor drugs.

 

Figure 1. Schematic representation of the gene editing strategy for generating FVB-Abcb1a&Abcb1b DKO (Mdr1a/b KO) Mice. In mice with an FVB genetic background, both the Abcb1a and Abcb1b genes are located on chromosome 5 and contain 28 exons. Abcb1a is located approximately 50kb upstream of Abcb1b. Using gene editing technology, the nucleotide sequence from exon 3 of the Abcb1a gene to exon 27 of the Abcb1b gene was knocked out.

● Research on blood-brain barrier permeability-related diseases;

● Research on multidrug resistance of anti-tumor drugs.

1. Detection of Abcb1a and Abcb1b gene expression in brain

Figure 2. Detection of Abcb1a and Abcb1b gene expression in brain tissue of FVB wild-type (WT) mice and FVB-Abcb1a&Abcb1b DKO (Mdr1a/b KO) mice. Quantitative PCR analysis revealed the expression of the Abcb1a and Abcb1b genes was absent in the brains of FVB-Abcb1a/Abcb1b DKO (Mdr1a/b KO) mice compared to WT mice.

References

[1] Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet. 2003;42(1):59-98.
[2] Seelig A. P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers. Front Oncol. 2020 Oct 26;10:576559.
[3] Robinson K, Tiriveedhi V. Perplexing Role of P-Glycoprotein in Tumor Microenvironment. Front Oncol. 2020 Mar 5;10:265.
[4] Chai AB, Callaghan R, Gelissen IC. Regulation of P-Glycoprotein in the Brain. Int J Mol Sci. 2022 Nov 24;23(23):14667.
[5] Buschman E, Lepage P, Gros P. P-glycoprotein homologues. Cancer Treat Res. 1994;73:17-39.
[6] Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene. 2003 Oct 20;22(47):7468-85.