Tissue distribution, gernder difference, ontogeny and chemical induction of multiple drug resistance genes (Mdr1a, Mdr1b, Mdr2) in mice

Abstract

Multiple drug resistance (Mdr) transporters are ABC transporters that efflux amphipathic cations out of cells, and thus protect them from xenobiotics, as well as cause resistance of some tumor cells to cancer chemotherapeutic drugs. There are three Mdr genes in mice: Mdr1a and Mdr1b, which transport xenobiotics; and Mdr2, which facilitates phospholipid excretion into bile. Very little is known about the regulation of the Mdr genes in vivo. Therefore the purpose of this study was to determine tissue distribution, gender differences, ontogeny, and chemical induction of the three Mdrs in mice. Our findings indicate that Mdr1a mRNA expression is highest in the gastrointestinal tract, Mdr1b mRNA expression is highest in ovary and placenta, and Mdr2 mRNA expression is highest in liver. Gender differences in expression of the three mice Mdrs were observed in several tissues: Mdr1a in kidney; Mdr1b in lung, kidney, and brain; and Mdr2 in lung. The ontogeny of mouse Mdr1a in duodenum; Mdr1b in brain, kidney and liver; as well as Mdr2 in liver share a similar developmental pattern; minimal mRNA levels are observed in neonatal stages, they gradually increase, and reach a plateau at about 30 days of age. None of the mRNA levels of the three transporters are readily increased by microsomal enzyme inducers. In conclusion, the three mice Mdr transporters are expressed in a tissue-specific pattern that are related to different functions, their expression has gender difference in several tissues, and none of the Mdr transporters are readily inducible.