@incollection{WolfKapelyukhScheeretal.2015,
  author    = {Wolf, C. Roland and Kapelyukh, Yury and Scheer, Nico and Henderson, Colin J.},
  title     = {Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs},
  editor    = {Wilson, Alan G. E.},
  publisher = {RSC Publ.},
  address   = {Cambridge},
  isbn      = {978-1-78262-778-4},
  doi       = {10.1039/9781782622376-00152},
  pages     = {152 -- 176},
  year      = {2015},
  abstract  = {The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.},
  language  = {en}
}
@article{StanleyHorsburghRossetal.2009,
  author    = {Stanley, Lesley A. and Horsburgh, Brian C. and Ross, Jillian and Scheer, Nico and Wolf, C. Roland},
  title     = {Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior},
  series = {Drug Metabolism Reviews},
  volume    = {41},
  journal   = {Drug Metabolism Reviews},
  number    = {1},
  publisher = {Taylor \& Francis},
  address   = {London},
  issn      = {1097-9883},
  doi       = {10.1080/03602530802605040},
  pages     = {27 -- 65},
  year      = {2009},
  language  = {en}
}
@article{StanleyHorsburghRossetal.2006,
  author    = {Stanley, Lesley A. and Horsburgh, Brian C. and Ross, Jillian and Scheer, Nico and Wolf, C. Roland},
  title     = {Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity},
  series = {Drug Metabolism Reviews},
  volume    = {38},
  journal   = {Drug Metabolism Reviews},
  number    = {3},
  issn      = {1097-9883},
  doi       = {10.1080/03602530600786232},
  pages     = {515 -- 597},
  year      = {2006},
  language  = {en}
}
@article{ScheerWolf2014,
  author    = {Scheer, Nico and Wolf, C. Roland},
  title     = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications},
  series = {Xenobiotica},
  volume    = {44},
  journal   = {Xenobiotica},
  number    = {2},
  publisher = {Taylor \& Francis},
  address   = {Abingdon},
  issn      = {1366-5928},
  doi       = {10.3109/00498254.2013.815831},
  pages     = {96 -- 108},
  year      = {2014},
  abstract  = {1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug-drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug-drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.},
  language  = {en}
}
@article{ScheerWolf2013,
  author    = {Scheer, Nico and Wolf, C. Roland},
  title     = {Xenobiotic receptor humanized mice and their utility},
  series = {Drug Metabolism Reviews},
  journal   = {Drug Metabolism Reviews},
  number    = {1},
  publisher = {Taylor \& Francis},
  address   = {London},
  issn      = {1097-9883},
  doi       = {10.3109/03602532.2012.738687},
  pages     = {110 -- 121},
  year      = {2013},
  language  = {en}
}
@article{ScheerSnaithWolfetal.2013,
  author    = {Scheer, Nico and Snaith, Mike and Wolf, C. Roland and Seibler, Jost},
  title     = {Generation and utility of genetically humanized mouse models},
  series = {Drug Discovery Today},
  volume    = {Vol 18},
  journal   = {Drug Discovery Today},
  number    = {23-24},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1359-6446},
  doi       = {10.1016/j.drudis.2013.07.007},
  pages     = {1200 -- 1211},
  year      = {2013},
  language  = {en}
}
@article{ScheerRossRodeetal.2008,
  author    = {Scheer, Nico and Ross, Jillian and Rode, Anja and Zevnik, Branko and Niehaves, Sandra and Faust, Nicole and Wolf, C. Roland},
  title     = {A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response},
  series = {Journal of Clinical Investigation},
  volume    = {118},
  journal   = {Journal of Clinical Investigation},
  number    = {9},
  issn      = {1558-8238},
  doi       = {https://doi.org/10.1172/JCI35483},
  pages     = {3228 -- 3239},
  year      = {2008},
  language  = {en}
}
@article{ScheerRossKapelyukhetal.2010,
  author    = {Scheer, Nico and Ross, Jillian and Kapelyukh, Yury and Rode, Anja and Wolf, C. Roland},
  title     = {In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice},
  series = {Drug Metabolism and Disposition},
  volume    = {38},
  journal   = {Drug Metabolism and Disposition},
  number    = {7},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-009X},
  doi       = {10.1124/dmd.109.031872},
  pages     = {1046 -- 1053},
  year      = {2010},
  abstract  = {Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.},
  language  = {en}
}
@article{ScheerKapelyukhRodeetal.2015,
  author    = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland},
  title     = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model},
  series = {Drug Metabolism and Disposition},
  volume    = {43},
  journal   = {Drug Metabolism and Disposition},
  number    = {11},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-009x},
  doi       = {10.1124/dmd.115.065656},
  pages     = {1679 -- 1690},
  year      = {2015},
  language  = {en}
}
@article{ScheerKapelyukhRodeetal.2012,
  author    = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland},
  title     = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines},
  series = {Molecular Pharmacology},
  volume    = {82},
  journal   = {Molecular Pharmacology},
  number    = {6},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/mol.112.080036},
  pages     = {1022 -- 1029},
  year      = {2012},
  abstract  = {Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.},
  language  = {en}
}