@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} } @incollection{HendersonWolfScheer2009, author = {Henderson, Colin J. and Wolf, C. Roland and Scheer, Nico}, title = {The use of transgenic animals to study drug metabolism}, series = {Handbook of Drug Metabolism. 2nd Edition}, booktitle = {Handbook of Drug Metabolism. 2nd Edition}, editor = {Woolf, Thomas F.}, publisher = {Informa Healthcare}, address = {New York}, isbn = {978-1-4200-7647-9}, pages = {637 -- 658}, 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} } @inproceedings{KazukiKobayashiHirabayashietal.2019, author = {Kazuki, Yasuhiro and Kobayashi, Kaoru and Hirabayashi, Masumi and Abe, Satoshi and Kajitani, Naoyo and Kazuki, Kanoko and Takehara, Shoko and Takiguchi, Masato and Satoh, Daisuke and Kuze, Jiro and Sakuma, Tetsushi and Kaneko, Takehito and Mashimo, Tomoji and Osamura, Minori and Hashimoto, Mari and Wakatsuki, Riko and Hirashima, Rika and Fujiwara, Ryoichi and Deguchi, Tsuneo and Kurihara, Atsushi and Tsukazaki, Yasuko and Senda, Naoto and Yamamoto, Takashi and Scheer, Nico and Oshimura, Mitsuo}, title = {Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism}, series = {PNAS Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, booktitle = {PNAS Proceedings of the National Academy of Sciences of the United States of America}, number = {8}, issn = {1091-6490}, doi = {10.1073/pnas.1808255116}, pages = {3072 -- 3081}, year = {2019}, language = {en} }