EXTRAHEPATIC EXPRESSION OF NAD(P)H-MENADIONE OXIDOREDUCTASE, UDP GLUCURONOSYLTRANSFERASE-1A6, MICROSOMAL ALDEHYDE DEHYDROGENASE, AND HEPATIC NUCLEAR FACTOR-1-ALPHA MESSENGER-RNAS IN CH CH AND 14COS/14COS MICE/

Oxidative stress-induced gene expression in liver of the untreated new born c(14CoS)/c(14CoS) mouse, as compared with that in the c(ch)/c(ch) wild-type mouse, appears to be caused by homozygous loss of the fumar ylacetoacetate hydrolase (Fah) gene on Chr 7 and absence of the FAH en zyme, which leads to increased levels of endogenous reactive oxygenate d metabolites (ROMs) formed in the tyrosine degradative pathway. In th ese mice almost all studies to date have been carried out in liver. We have examined the extrahepatic expression of four genes. Two genes ar e members of the [Ah] battery and induced by ROM-mediated oxidative st ress: NAD(P)H:menadione oxidoreductase (Nmo1) and UDP glucuronsyltrans ferase-1A6 (Ugt1a6). The other two genes are decreased in the livers o f 14CoS/14Cos mice as compared with that in ch/ch mice: microsomal ald ehyde dehydrogenase (Ahd3) and hepatocyte-specific nuclear factor-1 al pha HNF-alpha (Hnfl alpha). In liver plus nine extrahepatic tissues of untreated newborn 14CoS/14CoS mutant and ch/ch wild-type mice, we com pared NMO1, UGT1A6, AHD3 and HNF-1 alpha mRNA levels. Our results show a wide variation in extrahepatic tissue-specific expression of all fo ur transcripts and indicate that numerous differences exist in the ext rahepatic expression of these genes between 14Cos/14CoS and ch/ch mice . (C) 1997 Academic Press.