Choudhary D, Jansson I, Schenkman J B, Sarfarazi M, Stoilov I
Department of Pharmacology, Surgical Research Center, University of Connecticut Health Center, Farmington 06030, USA.
Arch Biochem Biophys. 2003 Jun 1;414(1):91-100. doi: 10.1016/s0003-9861(03)00174-7.
This study is the first systematic investigation of the gestational age-dependent and adult tissue-specific expression patterns of each known mouse CYP family (40 genes) using normalized cDNA panels and uniform reverse transcriptase polymerase chain reaction-based assays. Twenty-seven of the P450s were constitutively expressed during development. The number gradually increased through the phases of gastrulation E7 (n=14), neural patterning and somitogenesis E11 (n=17), organogenesis E15 (n=20), and fetal period E17 (n=21). Cyp2s1, Cyp8a1, Cyp20, Cyp21a1, Cyp26a1, Cyp46, and Cyp51 were detected in each of the four stages studied. Members of family CYP1 demonstrated complex, nonoverlapping embryonic patterns of expression, indicating that Cyp1a1 and Cyp1a2 may not compensate for Cyp1b1 deficiency associated with abnormal eye development. Multiple Cyp forms were found to be constitutively expressed in each of the adult tissues studied: liver (n=31), kidney (n=30), testis (n=26), lung (n=24), and heart (n=13). The tissue-specific P450-expression profiles reported in this study provide a reference for more focused analysis of the tissue-specific and developmental functions of the cytochrome P450 monooxygenases.
本研究首次使用标准化cDNA板和基于逆转录聚合酶链反应的统一检测方法，对每个已知小鼠CYP家族（40个基因）的胎龄依赖性和成体组织特异性表达模式进行了系统研究。27种细胞色素P450在发育过程中组成性表达。其数量在原肠胚形成期E7（n = 14）、神经模式形成和体节发生期E11（n = 17）、器官发生期E15（n = 20）以及胎儿期E17（n = 21）逐步增加。在所研究的四个阶段均检测到Cyp2s1、Cyp8a1、Cyp20、Cyp21a1、Cyp26a1、Cyp46和Cyp51。CYP1家族成员表现出复杂的、不重叠的胚胎表达模式，这表明Cyp1a1和Cyp1a2可能无法补偿与异常眼发育相关的Cyp1b1缺陷。在所研究的每个成体组织中均发现多种Cyp形式组成性表达：肝脏（n = 31）、肾脏（n = 30）、睾丸（n = 26）、肺（n = 24）和心脏（n = 13）。本研究报告的组织特异性P450表达谱为更深入分析细胞色素P450单加氧酶的组织特异性和发育功能提供了参考。
