Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2016; 22(16): 4109-4119
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4109
Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines
Gursimran Chandhok, Judit Horvath, Annu Aggarwal, Mohit Bhatt, Andree Zibert, Hartmut HJ Schmidt
Gursimran Chandhok, Andree Zibert, Hartmut HJ Schmidt, Klinik für Transplantationsmedizin, Universitätsklinikum Münster, D-48149 Münster, Germany
Judit Horvath, Institut für Humangenetik, Westfälische Wilhelms-Universität, D-48149 Münster, Germany
Annu Aggarwal, Mohit Bhatt, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai 400103, India
Author contributions: Chandhok G, Aggarwal A, Bhatt M, Zibert A and Schmidt HHJ designed the experiments; Chandhok G and Horvath J performed the experiments; Chandhok G interpreted the data and performed statistical analysis; Chandhok G, Zibert A and Schmidt HHJ wrote the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest associated with this manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hartmut HJ Schmidt, MD, Professor, Klinik für Transplantationsmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A14, D-48149 Münster, Germany. hepar@ukmuenster.de
Telephone: +49-251-8357935 Fax: +49-251-8357771
Received: December 5, 2015
Peer-review started: December 7, 2015
First decision: January 13, 2016
Revised: January 24, 2016
Accepted: February 20, 2016
Article in press: February 22, 2016
Published online: April 28, 2016
Processing time: 136 Days and 9.5 Hours
Core Tip

Core tip: Copper overload in Wilson disease (WD) is treated with anti-copper therapy. However, the effect of treatment has not been studied using human hepatic cells lacking the ATP7B copper transporter. Using a previously established ATP7B KO cell line, we generated stable mutant cell lines to study functional analysis and response to zinc (Zn) and D-penicillamine (DPA). All mutants showed individual response rates following copper and anti-copper treatment. Highest rescue from copper toxicity was observed after combined Zn and DPA treatment. The study provides novel insights into genotype-phenotype correlations and genotype-specific treatment of WD.