Fech-mut/Abcg2-null mice were generated by crossing Fech-mut mice with Abcg2-null mice and were backcrossed with Fech-mut mice for at least three generations. Abcg2-null mice, originally generated in Schinkel’s group (24), were obtained from Taconic Biosciences Inc. (Hudson, NY). Fech-mut mice were purchased from the Jackson Laboratory (Bar Harbor, ME), which were originally developed on the basis of a loss-of-function mutation of FECH (25, 26). Fech-mut/Abcg2-null mice were verified by polymerase chain reaction (PCR) genotyping of Fech mutation and mouse Abcg2. hPXR/Abcg2-null mice were generated by crossing hPXR mice with Abcg2-null mice and were backcrossed with hPXR mice for at least three generations. hPXR mice were originally generated by bacterial artificial chromosome transgenesis (32). hPXR/Abcg2-null mice were verified by PCR genotyping of human PXR, mouse Pxr, and mouse Abcg2. All mice (2- to 4-month-old, male) were kept under standard 12-hour light/dark cycle. The roles of ABCG2 in PPIX toxicities were determined in paired studies using WT versus Abcg2-null, hPXR versus hPXR/Abcg2-null, and Fech-mut versus Fech-mut/Abcg2-null mice, respectively. The handling of mice was in accordance with study protocols approved by the Institutional Animal Care and Use Committees of University of Pittsburgh and University of Kansas Medical Center.

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