Biomaterial Database

Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity. 2015

Frank J Gonzalez, and Zhong-Ze Fang, and Xiaochao Ma

National Institutes of Health, National Cancer Institute, Center for Cancer Research, Laboratory of Metabolism , Bethesda, MD 20892 , USA +1 301 496 9067 ; +1 301 496 8419 ; gonzalef@mail.nih.gov.

BACKGROUND The study of xenobiotic metabolism and toxicity has been greatly aided by the use of genetically modified mouse models and metabolomics. METHODS Gene knockout mice can be used to determine the enzymes responsible for the metabolism of xenobiotics in vivo and to examine the mechanisms of xenobiotic-induced toxicity. Humanized mouse models are especially important because there exist marked species differences in the xenobiotic-metabolizing enzymes and the nuclear receptors that regulate these enzymes. Humanized mice expressing CYPs and nuclear receptors including the pregnane X receptor, the major regulator of xenobiotic metabolism and transport were produced. With genetically modified mouse models, metabolomics can determine the metabolic map of many xenobiotics with a level of sensitivity that allows the discovery of even minor metabolites. This technology can be used for determining the mechanism of xenobiotic toxicity and to find early biomarkers for toxicity. CONCLUSIONS Metabolomics and genetically modified mouse models can be used for the study of xenobiotic metabolism and toxicity by: i) comparison of the metabolomics profiles between wild-type and genetically modified mice, and searching for genotype-dependent endogenous metabolites; ii) searching for and elucidating metabolites derived from xenobiotics; and iii) discovery of specific alterations of endogenous compounds induced by xenobiotics-induced toxicity.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013045	Species Specificity	The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.	Species Specificities,Specificities, Species,Specificity, Species
D015262	Xenobiotics	Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.	Xenobiotic
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055432	Metabolomics	The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions.	Metabonomics,Metabolomic,Metabonomic
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out