ArticleDrug metabolism and disposition: the biological fate of chemicals2012
RNA sequencing reveals dynamic changes of mRNA abundance of cytochromes P450 and their alternative transcripts during mouse liver development.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 61 citations in OpenAlex.
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- Metabolic differentiation of brushtail possum populations resistant and susceptible to plant toxins revealed via differential gene expression.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2025Article
- Aging Reduces ATP-Binding Cassette Transporter Expression in Brain Microvessels of Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Article
- Dynamic 3D genome reorganization during development and metabolic stress of the porcine liver.Cell discovery · 2022Article
- Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood.Acta pharmaceutica Sinica. B · 2022Article
- Effects of Overexpression of Fibroblast Growth Factor 15/19 on Hepatic Drug Metabolizing Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Dynamic Transcriptomic Profiling During Liver Development inFrontiers in physiology · 2022Article
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Alternative RNA Splicing in Fatty Liver Disease.Frontiers in endocrinology · 2021Review
- Acetaminophen-Induced Liver Injury Alters Expression and Activities of Cytochrome P450 Enzymes in an Age-Dependent Manner in Mouse Liver.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- A time-resolved multi-omic atlas of the developing mouse liver.Genome research · 2020Article
- Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice.Acta pharmaceutica Sinica. B · 2020Article
- Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis.The Journal of nutritional biochemistry · 2019Article
- RNA-Seq provides new insights on the relative mRNA abundance of antioxidant components during mouse liver development.Free radical biology & medicine · 2019Article
- Placental BCRP/ABCG2 Transporter Prevents Fetal Exposure to the Estrogenic Mycotoxin Zearalenone.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Molecular regulation of mammalian hepatic architecture.Current topics in developmental biology · 2019Review
- Chemical Activation of the Constitutive Androstane Receptor Leads to Activation of Oxidant-Induced Nrf2.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cytochromes P450 (P450s) are a superfamily of enzymes that have critical functions in liver to catalyze the biotransformation of numerous drugs. However, the functions of most P450s are not mature at birth, which can markedly affect the metabolism of drugs in newborns. Therefore, characterization of the developmental profiles and regulatory mechanisms of P450 expression is needed for more rational drug therapy of pediatric patients. An animal model is indispensable for studying the mechanisms of postnatal development of the P450s. Hence we used RNA sequencing (RNA-Seq) to provide a "true quantification" of mRNA expression of all P450s in mouse liver during development. Liver samples of male C57BL/6 mice at 12 different ages from prenatal to adulthood were used. Total mRNAs of the 103 mouse P450s displayed two rapid increasing stages after birth, reflecting critical functional transition of liver during development. Four ontogenic expression patterns were identified among the 71 significantly expressed P450s, which categorized genes into neonatal-, adolescent-, adolescent/adult-, and adult-enriched groups. The 10 most highly expressed subfamilies of mouse P450s in livers of adult mice were CYP2E, -2C, -2D, -3A, -4A, -2F, -2A, -1A, -4F, and -2B, which showed diverse expression profiles during development. The expression patterns of multiple members within a P450 subfamily were often classified to different groups. RNA-Seq also enabled the quantification of known transcript variants of CYP2C44, CYP2C50, CYP2D22, CYP3A25, and CYP26B1 and identification of novel transcripts for CYP2B10, CYP2D26, and CYP3A13. In conclusion, this study reveals the mRNA abundance of all the P450s in mouse liver during development and provides a foundation for mechanistic studies in the future.
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