To facilitate the study of Mrp2 function in integrated systems, Mrp2 deficient congenic rats were generated by transferring an Mrp2 gene with a premature stop codon from Mrp2-deficient Wistar rats to inbred Lewis.1W (LEW1.W) rats. RBF and GFR are similar in TR-neg. and control LEW.1W. With PAH infused at 2.8 and 5.6 mg/kg*h, FE of PAH was 6.9 ± 0.3 and 8.4 ± 0.5 in LEW.1W vs. 9.3 ± 0.6 and 11.9 ± 0.5 in TR-neg. LEW.1W (p < 0.001). In TR-neg. LEW.1W hepatic elimination of the Mrp2 substrate pravastatin was lower and its renal clearance was higher than in LEW.1W. These data indicate that generalized Mrp2-deficiency increases renal organic anion transport. To investigate renal Mrp2 deficiency, kidneys were cross-transplanted between both rat lines. Renal cortical gene expression profiling revealed 360 more than twofold induced genes and 277 more than twofold reduced genes in TR-neg. grafts transplanted into LEW.1W compared to syngeneically transplanted LEW.1W kidneys. In LEW.1W kidneys transplanted into TR-neg. LEW.1W expression of 351 genes was induced and expression of 340 genes was reduced more than twofold compared to syngeneically transplanted TR-neg. kidneys. TR-neg. LEW.1W allow tissue specific investigation of Mrp2 function and comparative studies without confounding large scale genetic strain differences.