TY  - JOUR
A1  - Dallas, Shannon
A1  - Salphati, Laurent
A1  - Gomez-Zepeda, David
A1  - Wanek, Thomas
A1  - Chen, Liangfu
A1  - Chu, Xiaoyan
A1  - Kunta, Jeevan
A1  - Mezler, Mario
A1  - Menet, Marie-Claude
A1  - Chasseigneaux, Stephanie
A1  - Declèves, Xavier
A1  - Langer, Oliver
A1  - Pierre, Esaie
A1  - DiLoreto, Karen
A1  - Hoft, Carolin
A1  - Laplanche, Loic
A1  - Pang, Jodie
A1  - Pereira, Tony
A1  - Andonian, Clara
A1  - Simic, Damir
A1  - Rode, Anja
A1  - Yabut, Jocelyn
A1  - Zhang, Xiaolin
A1  - Scheer, Nico
T1  - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model
JF  - Molecular Pharmacology
N2  - 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.
Y1  - 2016
U6  - http://dx.doi.org/10.1124/mol.115.102079
SN  - 1521-0111
VL  - 89
IS  - 5
SP  - 492
EP  - 504
PB  - ASPET
CY  - Bethesda, Md.
ER  - 
TY  - JOUR
A1  - Halbach, Thorsten
A1  - Scheer, Nico
T1  - Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins
JF  - Nucleic Acids Research
Y1  - 2000
U6  - http://dx.doi.org/10.1093/nar/28.18.3542
SN  - 1362-4962
VL  - 28
IS  - 18
SP  - 3542
EP  - 3550
ER  - 
TY  - JOUR
A1  - Hans, Stefan
A1  - Scheer, Nico
A1  - Riedl, Iris
A1  - Weizäcker, Elisabeth von
A1  - Blader, Patrick
A1  - Campos-Ortega, José A.
T1  - her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling
JF  - Development
Y1  - 2004
U6  - http://dx.doi.org/10.1242/dev.01167
SN  - 1477-9129
VL  - 131
IS  - 12
SP  - 2957
EP  - 2969
ER  - 
TY  - JOUR
A1  - Hasegawa, Maki
A1  - Kapelyukh, Yury
A1  - Tahara, Harunobu
A1  - Seibler, Jost
A1  - Rode, Anja
A1  - Krueger, Sylvia
A1  - Lee, Dongtao N.
A1  - Wolf, C. Roland
A1  - Scheer, Nico
T1  - Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line
JF  - Molecular Pharmacology
Y1  - 2011
U6  - http://dx.doi.org/10.1124/mol.111.071845
SN  - 1521-0111
VL  - 80
IS  - 33
SP  - 518
EP  - 528
PB  - ASPET
CY  - Bethesda, Md.
ER  - 
TY  - JOUR
A1  - Henderson, Colin J.
A1  - Mclaughlin, Lesley A.
A1  - Scheer, Nico
A1  - Stanley, Lesley A.
A1  - Wolf, C. Roland
T1  - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s
JF  - Molecular Pharmacology
Y1  - 2015
U6  - http://dx.doi.org/10.1124/mol.114.097394
SN  - 1521-0111
VL  - 87
IS  - 4
SP  - 733
EP  - 739
PB  - ASPET
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Henderson, Colin J.
A1  - Scheer, Nico
A1  - Wolf, C. Roland
T1  - Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man
JF  - Expert Review of Clinical Pharmacology
Y1  - 2009
U6  - http://dx.doi.org/10.1586/17512433.2.2.105
SN  - 1751-2441
VL  - 2
IS  - 2
SP  - 105
EP  - 109
PB  - Taylor & Francis
CY  - London
ER  - 
TY  - CHAP
A1  - Henderson, Colin J.
A1  - Wolf, C. Roland
A1  - Scheer, Nico
ED  - Woolf, Thomas F.
T1  - The use of transgenic animals to study drug metabolism
T2  - Handbook of Drug Metabolism. 2nd Edition
Y1  - 2009
SN  - 978-1-4200-7647-9
SP  - 637
EP  - 658
PB  - Informa Healthcare
CY  - New York
ER  - 
TY  - JOUR
A1  - Hough, Lindsay B.
A1  - Nalwalk, Julia W.
A1  - Ding, Xinxin
A1  - Scheer, Nico
T1  - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms
JF  - Drug Metabolism and Disposition
Y1  - 2015
U6  - http://dx.doi.org/10.1124/dmd.115.065490
SN  - 1521-009x
VL  - 43
IS  - 9
SP  - 1326
EP  - 1330
ER  - 
TY  - JOUR
A1  - Kapelyukh, Yury
A1  - Henderson, Colin James
A1  - Scheer, Nico
A1  - Rode, Anja
A1  - Wolf, Charles Roland
T1  - Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice
JF  - Drug Metabolism and Disposition
Y1  - 2019
U6  - http://dx.doi.org/10.1124/dmd.119.087718
IS  - Early view
ER  - 
TY  - CHAP
A1  - Kazuki, Yasuhiro
A1  - Kobayashi, Kaoru
A1  - Hirabayashi, Masumi
A1  - Abe, Satoshi
A1  - Kajitani, Naoyo
A1  - Kazuki, Kanoko
A1  - Takehara, Shoko
A1  - Takiguchi, Masato
A1  - Satoh, Daisuke
A1  - Kuze, Jiro
A1  - Sakuma, Tetsushi
A1  - Kaneko, Takehito
A1  - Mashimo, Tomoji
A1  - Osamura, Minori
A1  - Hashimoto, Mari
A1  - Wakatsuki, Riko
A1  - Hirashima, Rika
A1  - Fujiwara, Ryoichi
A1  - Deguchi, Tsuneo
A1  - Kurihara, Atsushi
A1  - Tsukazaki, Yasuko
A1  - Senda, Naoto
A1  - Yamamoto, Takashi
A1  - Scheer, Nico
A1  - Oshimura, Mitsuo
T1  - Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism
T2  - PNAS Proceedings of the National Academy of Sciences of the United States of America
Y1  - 2019
U6  - http://dx.doi.org/10.1073/pnas.1808255116
SN  - 1091-6490
VL  - 116
IS  - 8
SP  - 3072
EP  - 3081
ER  -