A novel humanized mouse lacking murine P450 oxidoreductase for studying human drug metabolism

Mercedes Barzi, Francis P. Pankowicz, Barry Zorman, Xing Liu, Xavier Legras, Diane Yang, Malgorzata Borowiak, Beatrice Bissig-Choisat, Pavel Sumazin, Feng Li and Karl-Dimiter Bissig ()
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Mercedes Barzi: Baylor College of Medicine
Francis P. Pankowicz: Baylor College of Medicine
Barry Zorman: Baylor College of Medicine
Xing Liu: Baylor College of Medicine
Xavier Legras: Baylor College of Medicine
Diane Yang: Baylor College of Medicine
Malgorzata Borowiak: Baylor College of Medicine
Beatrice Bissig-Choisat: Baylor College of Medicine
Pavel Sumazin: Baylor College of Medicine
Feng Li: Baylor College of Medicine
Karl-Dimiter Bissig: Baylor College of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Only one out of 10 drugs in development passes clinical trials. Many fail because experimental animal models poorly predict human xenobiotic metabolism. Human liver chimeric mice are a step forward in this regard, as the human hepatocytes in chimeric livers generate human metabolites, but the remaining murine hepatocytes contain an expanded set of P450 cytochromes that form the major class of drug-metabolizing enzymes. We therefore generated a conditional knock-out of the NADPH-P450 oxidoreductase (Por) gene combined with Il2rg − /− /Rag2 − /− /Fah − /− (PIRF) mice. Here we show that homozygous PIRF mouse livers are readily repopulated with human hepatocytes, and when the murine Por gene is deleted (

Date: 2017
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DOI: 10.1038/s41467-017-00049-x

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