Sex- and tissue-specific expression of a cytochrome P450 2C2-luciferase transgene

To study the transcriptional regulation of the rabbit cytochrome P450 2C2 gene (CYP2C2), transgenic mice were generated using a DNA fragment containing the CYP2C2 5'-flanking region fused to a luciferase reporter gene. In one of three transgenic lines, this transgene was expressed in the liver and at a lower level in the kidney, similar to the tissue-specific pattern of this gene in rabbits. Unlike expression in rabbits, the transgene was expressed in a male-specific pattern in liver and kidney, and in the brain of both sexes. Expression of the transgene in male mice was repressed after castration, while expression in females was stimulated after testosterone treatment and periodic injection of rat growth hormone (GH). The expression of this transgene was also regulated developmentally in the liver. These results suggest that this 3500 bp of CYP2C2 5'-flanking region contains the basal transcriptional regulation elements for tissue-specific and developmental expression. Although a position effect can not be ruled out, this transgene may also include the cis-regulatory element for sexual dimorphic expression.