TY  - JOUR
A1  - Seibler, Jost
A1  - Zevnik, Branko
A1  - Küter-Luks, Birgit
A1  - Andreas, Susanne
A1  - Kern, Heidrun
A1  - Hennek, Thomas
A1  - Rode, Anja
A1  - Heimann, Cornelia
A1  - Faust, Nicole
A1  - Kauselmann, Gunther
A1  - Schoor, Michael
A1  - Jaenisch, Rudolf
A1  - Rajewsky, Klaus
A1  - Kühn, Ralf
A1  - Schwenk, Frieder
T1  - Rapid generation of inducible mouse mutants
JF  - Nucleic Acids Research
Y1  - 2003
U6  - http://dx.doi.org/10.1093/nar/gng012
SN  - 1362-4962
VL  - 33
IS  - 4
SP  - e12
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Balimane, Praveen
A1  - Hayward, Michael D.
A1  - Buechel, Sandra
A1  - Kauselmann, Gunther
A1  - Wolf, C. Roland
T1  - Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line
JF  - Drug Metabolism and Disposition
N2  - The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.
Y1  - 2012
U6  - http://dx.doi.org/10.1124/dmd.112.047605
SN  - 1521-0111
VL  - 40
IS  - 11
SP  - 2212
EP  - 2218
PB  - ASPET
CY  - Bethesda, Md.
ER  -