The Ontogeny of Novel Cytochrome P450 Gene Isoforms during Postnatal Liver Maturation in Mice

This article has not been copyedited and formatted. The final version may differ from this version. ABSTRACT The ontogeny of the first four families of cytochrome P450s (Cyp1-4) can affect the biotransformation of drugs and dietary chemicals in liver resulting in unique pharmacological reactions in children. As genome-scale investigations have identified many novel Cyp isoforms recently, it is critical to perform a systematic characterization of these Cyps during liver development. In this study, livers were collected from C57BL/6 mice at 2-days before birth and various postnatal ages (from 0-to 45-days of age). The mRNAs of 75 Cyp isoforms (Cyp1-4) were quantified by bDNA assay and RT-PCR. Over half of the mouse Cyps are conserved for humans, but there are more isoforms in mice. The Cyp mRNAs increased after birth in mouse liver, forming four distinct ontogeny patterns. The majority of Cyps form a total of 8 genomic clusters, namely, Cyp1a1 and 1a2 on chr 9 (cluster 1), Cyp2a-2b-2f-2g-2t genes on chr 7 (cluster 2), Cyp2c genes on chr 19 (cluster 3), Cyp2d genes on chr 15 (cluster 4), Cyp2j genes on chr 4 (cluster 5), Cyp3a genes on chr 5 (cluster 6), Cyp4a-4b-4x genes on chr 4 (cluster 7), and Cyp4f genes on chr 17 (cluster 8). Some Cyp isoforms within the same genomic cluster showed similar ontogeny patterns. In conclusion, the present study has revealed 4 patterns of ontogeny of Cyps in liver, and showed that many Cyps within a genomic cluster share similar ontogeny patterns, suggesting that some Cyps within a cluster are likely regulated by a common pathway during liver development.