Developmental regulation of flavin-containing monooxygenase (FMO) form 1 and form 2 mRNA in fetal and neonatal rabbit Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/mk61rk855

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  • The mammalian FMO represents a multigene family which oxygenates a large number of xenobiotics. No physiological role has been determined for FMO, although synthesis of disulfide bonds and detoxification of dietary chemicals have been suggested. Five FMO gene subfamilies, each containing a single gene, have been identified. In this study, we determined the patterns of fetal and neonatal development of FMO1 and FMO2 in rabbit liver and lung. The expression of two major isoforms, FMO1 and FMO2, in fetal and neonatal animals were characterized at the steady state levels of mRNA. Northern and slot blot analyses were performed with cDNA probes for each isoform to provide a qualitative and quantitative profile. In order to relate developmental changes in FMO to the metabolism of xenobiotics for which lung is a target organ, the developmental expression of lung FMO (FMO2) mRNA is compared to rabbit CYP2B4 and CYP4B1 which are the major constitutive P450s in lung. The results show that the expression of FMO1 and FMO2 is tissue-dependent, although the mechanisms controlling the mRNA expression, such as rate of transcription, processing of primary RNA, efficiencies of nucleocytoplasmic transport and stability of RNA in the cytoplasm, are still unknown. The results indicate that the early development- and tissue-specific expression patterns of mRNA for FMO1 and FMO2 might play a significant role in the target organ toxicity of xenobiotics in the rabbit fetus and neonate.
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