A 346-BASE PAIR REGION OF THE MOUSE GAMMA-GLUTAMYL-TRANSPEPTIDASE TYPE-II PROMOTER CONTAINS SUFFICIENT CIS-ACTING ELEMENTS FOR KIDNEY-RESTRICTED EXPRESSION IN TRANSGENIC MICE

The mouse gamma-glutamyl transpeptidase (GGT) gene encodes seven disti nct mRNAs that are transcribed from seven separate promoters, Type II mRNA is the most abundant in kidney, We have developed a cell line wit h features of renal proximal tubular cells which expresses GGT mRNA ty pes with a pattern similar to that of mouse kidney, Because a 346-bp s equence from the type II promoter directed the highest level of CAT ac tivity in these cells, this region was used to drive the expression of a beta-galactosidase reporter gene in transgenic mice, Two transgenic mouse lines expressed beta-galactosidase limited to the renal proxima l tubules, Site-directed deletions within this 346-bp promoter region demonstrated that cis-elements containing the consensus binding sites for AP2, a glucocorticoid response element (GRE)-like element, and the initiator region were required for transcriptional activity and were not additive, Purified AP2 bound and footprinted the AP2 consensus reg ion, making it likely that transcription from the GGT type II promoter is regulated in part by AP2. These data suggest that transcription of the type II promoter requires multiple protein DNA interactions invol ving at least an AP2 element, and probably a GRE-like element and the initiator region.