Drug-metabolizing Enzyme, Transporter, and Nuclear Receptor Genetically Modified Mouse Models
Overview
Authors
Affiliations
Determining the in vivo significance of a specific enzyme, transporter, or xenobiotic receptor in drug metabolism and pharmacokinetics may be hampered by gene multiplicity and complexity, levels of expression, and interaction between various components involved. The development of knockout (loss-of-function) and transgenic (gain-of-function) mouse models opens the door to the improved understanding of gene function in a whole-body system. There is also growing interest in the development of humanized mice to overcome species differences in drug metabolism and disposition. This review, therefore, aims to summarize and discuss some successful examples of drug-metabolizing enzyme, transporter, and nuclear-receptor genetically modified mouse models. These genetically modified mouse models have been proven as invaluable models for understanding in vivo function of drug-metabolizing enzymes, transporters, and xenobiotic receptors in drug metabolism and transport, as well as predicting potential drug-drug interaction and toxicity in humans. Nevertheless, concerns remain about interpretation of data obtained from such genetically modified mouse models, in which the expression of related genes is altered significantly.
Wang Y, Tu M, Yu A Front Pharmacol. 2024; 15:1423416.
PMID: 39114355 PMC: 11303158. DOI: 10.3389/fphar.2024.1423416.
Assessing cytochrome P450 function using genetically engineered mouse models.
Hannon S, Ding X Adv Pharmacol. 2022; 95:253-284.
PMID: 35953157 PMC: 10544722. DOI: 10.1016/bs.apha.2022.05.008.
Effects of total parenteral nutrition on drug metabolism gene expression in mice.
Ferrucci-Da Silva C, Zhan L, Shen J, Kong B, Campbell M, Memon N Acta Pharm Sin B. 2020; 10(1):153-158.
PMID: 31993312 PMC: 6976970. DOI: 10.1016/j.apsb.2019.10.012.
Clerbaux L, Paini A, Lumen A, Osman-Ponchet H, Worth A, Fardel O Environ Int. 2019; 126:659-671.
PMID: 30856453 PMC: 6441651. DOI: 10.1016/j.envint.2019.03.003.
The safety evaluation of food flavouring substances: the role of metabolic studies.
Smith R, Cohen S, Fukushima S, Gooderham N, Hecht S, Guengerich F Toxicol Res (Camb). 2018; 7(4):618-646.
PMID: 30090611 PMC: 6062396. DOI: 10.1039/c7tx00254h.