@article{DallasSalphatiGomezZepedaetal.2016,
  author    = {Dallas, Shannon and Salphati, Laurent and Gomez-Zepeda, David and Wanek, Thomas and Chen, Liangfu and Chu, Xiaoyan and Kunta, Jeevan and Mezler, Mario and Menet, Marie-Claude and Chasseigneaux, Stephanie and Decl{\`e}ves, Xavier and Langer, Oliver and Pierre, Esaie and DiLoreto, Karen and Hoft, Carolin and Laplanche, Loic and Pang, Jodie and Pereira, Tony and Andonian, Clara and Simic, Damir and Rode, Anja and Yabut, Jocelyn and Zhang, Xiaolin and Scheer, Nico},
  title     = {Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model},
  series = {Molecular Pharmacology},
  volume    = {89},
  journal   = {Molecular Pharmacology},
  number    = {5},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/mol.115.102079},
  pages     = {492 -- 504},
  year      = {2016},
  abstract  = {Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp-/-) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.},
  language  = {en}
}
@article{HalbachScheer2000,
  author    = {Halbach, Thorsten and Scheer, Nico},
  title     = {Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins},
  series = {Nucleic Acids Research},
  volume    = {28},
  journal   = {Nucleic Acids Research},
  number    = {18},
  issn      = {1362-4962},
  doi       = {10.1093/nar/28.18.3542},
  pages     = {3542 -- 3550},
  year      = {2000},
  language  = {en}
}
@article{HansScheerRiedletal.2004,
  author    = {Hans, Stefan and Scheer, Nico and Riedl, Iris and Weiz{\"a}cker, Elisabeth von and Blader, Patrick and Campos-Ortega, Jos{\´e} A.},
  title     = {her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling},
  series = {Development},
  volume    = {131},
  journal   = {Development},
  number    = {12},
  issn      = {1477-9129},
  doi       = {10.1242/dev.01167},
  pages     = {2957 -- 2969},
  year      = {2004},
  language  = {en}
}
@article{HasegawaKapelyukhTaharaetal.2011,
  author    = {Hasegawa, Maki and Kapelyukh, Yury and Tahara, Harunobu and Seibler, Jost and Rode, Anja and Krueger, Sylvia and Lee, Dongtao N. and Wolf, C. Roland and Scheer, Nico},
  title     = {Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line},
  series = {Molecular Pharmacology},
  volume    = {80},
  journal   = {Molecular Pharmacology},
  number    = {33},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/mol.111.071845},
  pages     = {518 -- 528},
  year      = {2011},
  language  = {en}
}
@article{HendersonMclaughlinScheeretal.2015,
  author    = {Henderson, Colin J. and Mclaughlin, Lesley A. and Scheer, Nico and Stanley, Lesley A. and Wolf, C. Roland},
  title     = {Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s},
  series = {Molecular Pharmacology},
  volume    = {87},
  journal   = {Molecular Pharmacology},
  number    = {4},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-0111},
  doi       = {10.1124/mol.114.097394},
  pages     = {733 -- 739},
  year      = {2015},
  language  = {en}
}
@article{HendersonScheerWolf2009,
  author    = {Henderson, Colin J. and Scheer, Nico and Wolf, C. Roland},
  title     = {Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man},
  series = {Expert Review of Clinical Pharmacology},
  volume    = {2},
  journal   = {Expert Review of Clinical Pharmacology},
  number    = {2},
  publisher = {Taylor \& Francis},
  address   = {London},
  issn      = {1751-2441},
  doi       = {10.1586/17512433.2.2.105},
  pages     = {105 -- 109},
  year      = {2009},
  language  = {en}
}
@article{HoughNalwalkDingetal.2015,
  author    = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico},
  title     = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms},
  series = {Drug Metabolism and Disposition},
  volume    = {43},
  journal   = {Drug Metabolism and Disposition},
  number    = {9},
  issn      = {1521-009x},
  doi       = {10.1124/dmd.115.065490},
  pages     = {1326 -- 1330},
  year      = {2015},
  language  = {en}
}
@article{KapelyukhHendersonScheeretal.2019,
  author    = {Kapelyukh, Yury and Henderson, Colin James and Scheer, Nico and Rode, Anja and Wolf, Charles Roland},
  title     = {Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice},
  series = {Drug Metabolism and Disposition},
  journal   = {Drug Metabolism and Disposition},
  number    = {Early view},
  doi       = {10.1124/dmd.119.087718},
  pages     = {43 Seiten},
  year      = {2019},
  language  = {en}
}
@article{LawsonScheerPhametal.2001,
  author    = {Lawson, Nathan D. and Scheer, Nico and Pham, Van N. and Kim, Ceol-Hee and Chitnis, Ajay B. and Campos-Ortega, Jos{\´e} A. and Weinstein, Brant M.},
  title     = {Notch signaling is required for arterial-venous differentiation during embryonic vascular development},
  series = {Development},
  volume    = {128},
  journal   = {Development},
  number    = {19},
  issn      = {1477-9129},
  pages     = {3675 -- 3683},
  year      = {2001},
  language  = {en}
}
@article{LempiaeinenCouttetBolognanietal.2012,
  author    = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.},
  title     = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion},
  series = {Toxicological Sciences},
  volume    = {131},
  journal   = {Toxicological Sciences},
  number    = {2},
  publisher = {Oxford University Press},
  address   = {Oxford},
  issn      = {1094-2025},
  doi       = {10.1093/toxsci/kfs303},
  pages     = {375 -- 386},
  year      = {2012},
  abstract  = {The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.},
  language  = {en}
}