• Mdr1 is predominantly expressed in the intestine, blood-brain barrier, blood-testis barrier, and adrenal glands, pregnant uterus, and ovaries. These P-glycoproteins actively pump drugs out of cells, contributing to multidrug resistance in tumors. Their absence disrupts blood-brain barrier protection and increases systemic drug exposure.
• The genome sequences between ratMdr1agene andMdr1bgene were depleted in B-Mdr1 KO rats. As a result, rat MDR1 protein will not be expressed anymore.
• Mdr1 mRNA and protein were detectable only in wild-type SD rats, but not in B-Mdr1 KO rats.

Suggestion:

• This model is valuable for studying CNS drug delivery, neurotoxicology, oral bioavailability, and mechanisms of multidrug resistance.

Gene targeting strategy for B-Mdr1 KO rats.The genome sequences between ratMdr1agene andMdr1bgene were depleted in B-Mdr1 KO rats. As a result, rat MDR1 protein will not be expressed anymore.

Mdr1mRNA expression in wild-type SD rats and B-Mdr1 KO rats by RT-PCR. Liver RNA were isolated from wild-type SD rats (+/+) and B-Mdr1 KO rats (-/-), then cDNA libraries were synthesized by reverse transcription, followed by PCR with ratMdr1primers. RatMdr1mRNA was detectable only in wild-type SD rats, but not in B-Mdr1 KO rats.

Western blot analysis of Mdr1 protein expression in B-Mdr1 KO rats. Various tissue lysates were collected from wild-type SD rats (+/+) and B-Mdr1 KO rats (-/-), and then analyzed by western blot with anti-Mdr1 antibody (abcam, ab170904). 40 μg total proteins were loaded for western blotting analysis. Mdr1 was not detectable in B-Mdr1 KO rats.