ESTABLISHMENT OF TRANSGENIC MICE CARRYING HUMAN FETUS-SPECIFIC CYP3A7

CYP3A7 is a cytochrome P450 isozyme expressed prenatally in humans, Si x lines of mice transgenic for human CYP3A7 were established by microi njecting a CYP3A7 cDNA downstream of a mouse metallothionein-1 promote r gene into the male pronucleus of fertilized mouse oocytes. The inser ted CYP3A7 transgene was expressed at a mRNA level in a variety of tis sues including the liver, kidney, lung, spleen, testis, small intestin e, thymus, brain, skin, and heart of adult mice. The protein expressio n of the transgene was also detected in the liver and testis of line M 10 mice. A significantly higher level of total testosterone in the ser um was found in line M10 male mice. In addition, this transgenic line exhibited weight increases in the liver, kidney, and uterus but a decr ease in the testis (P < 0.01). The transcript of the integrated CYP3A7 gene possessed the ability to activate aflatoxin B-1 in Ames test in which the his(+) revertants of Salmonella typhimurium TA100 per plate were significantly higher (P < 0.01) when liver microsomes of line M10 transgenic mice were used. This result demonstrates that the CYP3A7 g ene has been integrated into the mouse genome and translated into a ca talytically active enzyme. These transgenic mice are expected to give useful information for studies on fetal toxicities in humans. (C) 1996 Academic Press, Inc.