The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

Abstract

The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in relation to understanding the normal physiological function of the mdr multigene family.

Resolution of P‐glycoprotein and non‐P‐glycoprotein effects on drug permeability using intestinal tissues from mdr1a (−/−) mice

“…The pro®le of PGP expression in rodents is complicated by the presence of two genes mdr1a and mdr1b (Croop et al, 1989). However, both absorptive (A-B) permeability and the degree of e ux of paclitaxel and etoposide was essentially identical in tissues from mdr1a (7/7) and mdr1a/1b (7/7) animals, suggesting that mdr1b is not involved in drug e ux in the intestine.…”

“…Although mdr1b is absent from the intestine of normal mice (Croop et al, 1989), the expression of this gene is known to be upregulated in the kidney and liver of mdr1a (7/7) mice (Schinkel et al, 1994). To investigate potential compensatory e ects in intestine the transport of paclitaxel and etoposide was measured in intestine from mice in which both mdr1a and mdr1b expression had been ablated (Figure 7).…”

“…One of the key components of this barrier is P-glycoprotein (PGP), a member of the ABC transporter family (Hunter & Hirst, 1997), that is coded for by the MDR1 gene in humans and by the mdr1a and mdr1b genes in rodents, only mdr1a being found in intestine (Croop et al, 1989). PGP is a polyspeci®c transporter that can pump a very broad range of substrates, including vinca alkaloids, anthracyclines, digoxin, epipodophyllotoxins and b-adrenergic agonists, into the gut lumen (Hunter & Hirst, 1997).…”

Site-dependent contributions of P-glycoprotein and CYP3A to cyclosporin A absorption, and effect of dexamethasone in small intestine of mice

“…Polymerase chain reaction (PCR) was carried out in a final volume of 20 mL, containing 1 mL of RT reaction mixture, 50 mM KCl, 20 mM Tris-HCl (pH 8.3), 2.5 mM MgCl 2 , 0.2 mM each of dATP, dCTP, dGTP, and dTTP, 1 mM each of the mixed oligonucleotide primers, and 1 unit of Taq DNA polymerase (Gibco-BRL). Reported primers were used for mouse mdr1a (576 bp) [28], mouse mdr1b (486 bp) [29], mouse CYP3A (670 bp) [29], and mouse ß-actin (456 bp) [30]. Each cycle consisted of 45 s at 94 8C, 60 s at 60 8C, and 75 s at 72 8C for mdr1a and mdr1b, 45 s at 94 8C, 60 s at 56 8C, and 75 s at 72 8C for CYP3A, and 45 s at 94 8C, 60 s at 58 8C, and 75 s at 72 8C for ß-actin.…”

P-glycoprotein (encoded by multidrug resistance genes) is not required for interleukin-2 secretion in mice and humans

“…Although mdr1a and mdr1b are largely overlapping, they differ to some extent in drug transport capacity and tissue distribution. 5,16,17 The cells of the immune system appear to have similar levels of both mdr1a and mdr1b.…”