In summary, we have used a transgenic mouse model to study the transcriptional activity of the nACh receptor β4 subunit gene promoter. As described above, the activity of the β4/β-gal transgene used in this study paralleled, for the most part, endogenous β4 subunit mRNA expression both spatially and temporally. These results indicate that the 2.3-kilobase pair fragment of the nACh receptor β4 subunit 5′-flanking DNA contains transcriptional regulatory elements critical for appropriate cell-type-specific and developmentally regulated expression of the β4 subunit gene. Although the precise regulatory elements within the 2.3-kilobase pair region responsible for the in vivo activity of the β4 promoter have not been determined, strong candidates are the CT and CA boxes that we previously characterized in cell culture systems. The significance of these elements in vivo is currently being pursued. However, it is clear that the 2.3-kilobase pair fragment does not contain all of the required positive regulatory elements that govern expression of the β4 gene, as there are regions of the brain that express relatively high levels of the β4 gene but in which no transgene
