DIFFERENTIAL DEVELOPMENTAL AND TISSUE-SPECIFIC REGULATION OF EXPRESSION OF THE GENES ENCODING 3 MEMBERS OF THE FLAVIN-CONTAINING MONOOXYGENASE FAMILY OF MAN, FMO1, FM03 AND FM04

We have previously described the isolation and sequencing of cDNA clon es encoding flavin-containing monooxygenases (FMOs) 1 and 4 of man [Do lphin, 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 th e amino acid sequence deduced from it differ substantially from those previously reported for this member of the FMO family of man. In addit ion, we have investigated, by quantitative RNase protection assays, th e expression in several foetal and adult human tissues of genes encodi ng FMO1, FMO3 and FMO4. Our results demonstrate that, in the adult, FM O1 is expressed in kidney but not in liver, whereas in the foetus it i s expressed in both organs. The lack of expression of FMO1 in adult hu man liver is in marked contrast to the situation in other mammals, suc h as pig and rabbit, in which FMO1 constitutes a major form of the enz yme in the liver of the adult animal. The mRNA encoding FMO3 is abunda nt in adult liver and is also present, in low abundance, in some foeta l tissues. Thus, FMO1 and FMO3 are both subject to developmental and t issue-specific regulation, with a developmental switch in the expressi on of the genes taking place in the liver. FMO4 mRNA is present in low abundance in several foetal and adult tissues and thus the correspond ing gene appears to be expressed constitutively.