Abstract

Cytochrome P450s are a superfamily of enzymes, which have critical functions in liver to catalyze the biotransformation of numerous drugs. However, the functions of most CYPs 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 CYP 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 Cyps. Hence we used RNA-Seq to provide a "true-quantification" of mRNA expression of all Cyps 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 Cyps 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 Cyps, which categorized genes into neonatal-, adolescent-, adolescent/adult-, and adult-enriched groups. The 10 most highly expressed subfamilies of mouse Cyps 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 Cyp subfamily were often classified to different groups. RNA-Seq also enabled the quantification of known transcript variants of Cyp2c44, 2c50, 2d22, 3a25, and 26b1, and to identify novel transcripts for Cyp2b10, 2d26, and 3a13. In conclusion, this study reveals the mRNA abundance of all the Cyps in mouse liver during development, and provides a foundation for mechanistic studies in the future.