1995 Volume 10 Issue supplement Pages 122-125
Six lines of mice transgenic for the human fetus-specific CYP3A7 have been established using microinjection method. The CYP3A7 transgene was found to be integrated into mouse genome randomly with different copy numbers, ranging from 1 to several hundreds. Northern blot analysis revealed that the transgene expressed in livers only in line M10, whereas all except line M10 expressed the transgene in kidneys. In line M10 mice, increases of weight were observed in the liver, kidney, and uterus while the testis was found to decrease in weight, comparing to their non-transgenic littermates. In addition, serum total testosterone was significantly elevated in line M10 mice, indicating the involvement of CYP3A7 in the metabolism of steroid hormones.
The CYP3A7 expressed in the transgenic mice activated AFB1 in vivo resulting in significant increases of DNA damage in the livers and kidneys in line M10 and M2 mice, respectively. The data of midazolam metabolism using line M 10 mice also revealed that CYP3A7 mainly catalyzed hydroxylation at 1' position, similar to CYP3A4 which is an adult-specific isozyme in the CYP3A subfamily.
