EXPRESSION OF AN AQP2 CRE RECOMBINASE TRANSGENE IN KIDNEY AND MALE REPRODUCTIVE-SYSTEM OF TRANSGENIC MICE

A transgenic mouse approach was used to examine the mechanism of princ ipal cell-specific expression of aquaporin-2 (AQP2) within the renal c ollecting duct. RT-PCR and immunocytochemistry revealed that murine AQ P2 was expressed in principal cells in the renal collecting duct, epit helial cells of the vas deferens, and seminiferous tubules within test is. The vas deferens expression was confirmed in rats. RT-PCR and immu nocytochemistry showed that 14 kb of the human 5'-flanking region conf ers specific expression of a nucleus-targeted and epitope-tagged Cre r ecombinase in the principal cells within the renal collecting duct, in the epithelial cells of the vas deferens, and within the testis of tr ansgenic mice. These results suggest that cell-specific expression of AQP2 is mediated at the transcriptional level and that 14 kb of the hu man AQP2 5'-flanking region contain cis elements that are sufficient f or cell-specific expression of AQP2. Finally, renal principal cell exp ression of Cre recombinase is the first step in achieving cell-specifi c gene knockouts, thereby allowing focused examination of gene functio n in this cell type.