In mice, both approaches are highly developed. In the first approach, a 1-cell embryo at the pronuclear stage is injected with a transgene. The transgene contains the coding region, often in the form of a complementary DNA of the protein of interest, coupled to a promoter that drives expression. The promoter is typically not the promoter of the native gene but rather a heterologous promoter chosen because of its strength or pattern of expression. However, transgenes may also consist of segments of genomic DNA that contain the gene of interest, often in the form of bacterial artificial chromosomes or P1 artificial chromosomes, in which case the transgene is driven by its native promoter and enhancers. The injected transgene integrates randomly, typically in multiple copies at a single site. Because no corresponding allele exists on the homologous chromosome opposite the integration site, these mice are usually called hemizygous. Because the heterologous promoters chosen are typically strong, the transgenic protein is often expressed at levels higher than would be present physiologically. In addition, because the mouse typically contains its own endogenous version
