Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FM03 and FM04
Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FM03 and FM04
复制标题
DOI：
10.1111/j.1432-1033.1996.00683.x
复制
发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
Phillips, IR
中科院分区：
文献类型：
--
作者：
Dolphin, CT;Cullingford, TE;Phillips, IR
我们之前已经描述了编码人类含黄素单加氧酶（FMO）1和4的cDNA克隆的分离和测序[海豚，C.，Shephard，E.一、Povey，S.，帕尔默角，澳-地N.一、齐格勒，D. M.，阿耶什河，史密斯河L. &菲利普斯，I. R.（1991）J.Biol.Chem.266，12379-12385;海豚，C.，Shephard，E.一、Povey，S.，史密斯河L. &菲利普斯，I. R.等（1992）Biochem.J.287，261-267]。我们分离了人FMO 3的cDNA，其序列和推导的氨基酸序列与以前报道的人FMO家族成员的序列有很大的不同。此外，我们还通过定量RNA酶保护试验研究了编码FMO 1、FMO 3和FMO 4的基因在几种胎儿和成人组织中的表达。我们的研究结果表明，在成人中，FMO 1在肾脏中表达，但在肝脏中不表达，而在胎儿中，它在两个器官中表达。FMO 1在成年人肝脏中缺乏表达与其它哺乳动物如猪和兔中的情况形成鲜明对比，在其它哺乳动物中，FMO 1构成成年动物肝脏中酶的主要形式。编码FMO 3的mRNA在成人肝脏中丰富，并且也以低丰度存在于一些胎儿组织中。因此，FMO 1和FMO 3都受到发育和组织特异性调节，在肝脏中发生基因表达的发育转换。FMO 4 mRNA以低丰度存在于几种胎儿和成人组织中，因此相应的基因似乎组成型表达。
We have previously described the isolation and sequencing of cDNA clones encoding flavin-containing monooxygenases (FMOs) 1 and 4 of man [Dolphin, C., Shephard, E. A., Povey, S., Palmer, C. N. A., Ziegler, D. M., Ayesh, R., Smith, R. L. & Phillips, I. R. (1991) J. Biol. Chem. 266, 12379-12385; Dolphin, C., Shephard, E. A., Povey, S., Smith, R. L. & Phillips, I. R. (1992) Biochem. J. 287, 261-267]. We present here the isolation of a cDNA for FMO3 of man. The sequence of this cDNA and the amino acid sequence deduced from it differ substantially from those previously reported for this member of the FMO family of man. In addition, we have investigated, by quantitative RNase protection assays, the expression in several foetal and adult human tissues of genes encoding FMO1, FMO3 and FMO4. Our results demonstrate that, in the adult, FMO1 is expressed in kidney but not in liver, whereas in the foetus it is expressed in both organs. The lack of expression of FMO1 in adult human liver is in marked contrast to the situation in other mammals, such as pig and rabbit, in which FMO1 constitutes a major form of the enzyme in the liver of the adult animal. The mRNA encoding FMO3 is abundant in adult liver and is also present, in low abundance, in some foetal tissues. Thus, FMO1 and FMO3 are both subject to developmental and tissue-specific regulation, with a developmental switch in the expression of the genes taking place in the liver. FMO4 mRNA is present in low abundance in several foetal and adult tissues and thus the corresponding gene appears to be expressed constitutively.