The house musk shrew (Suncus murinus): a unique animal with extremely low level of expression of mRNAs for CYP3A and flavin-containing monooxygenase

Expression of drug-metabulizing enzymes including cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in various tissues of Suncus murinus (Suncus) were examined. Northern blot analysis showed that mRNAs hybridiza ble with cDNAs for rat CYP1A2, human CYP2A6, rat CYP2B1, human CYP2C8, huma n CYP2D6, rat CYP2E1, human CYP3A4 and rat CYP3A1 were expressed in various tissues from Suncus. The mRNA level of CYP2A in the Suncus lung was very h igh. Furthermore, it was found that the level of CYP2A mRNA in thr Suncus l ung was higher compared to the Suncus liver. The expression level of mRNA h ybridizable with cDNA for human CYP3A4 was very low. The presence of CYP3A gene in Suncus was proven by the induction of the CYP with dexamethasone. V ery low expression levels of mRNAs hybridizable with cDNAs for rat FMO1, ra t FMO2, rat FMO3 and rat FMO5 were also seen in Suncus liver. No apparent h ybridization band appeared when human FMO4 cDNA was used as a probe. The he patic expression of mRNAs hybridizable with cDNAs for UDP-glucuronosyltrans ferase 1*6, aryl sulfotransferase, glutathione S-transferase 1, carboxyeste rase and microsomal epoxide hydrolase in the Suncus were observed. These re sults indicate that the Suncus is a unique animal species in that mRNAs for CYP3A and FMO are expressed at very low Levels. (C) 2000 Elsevier Science Inc. All rights reserved.