The UT-A Urea Transporter Promoter UT-Aα Targets Principal Cells of the Renal Inner Medullary Collecting Duct

摘要

The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are localized to the terminal portion of the inner medullary collecting duct (IMCD). In this manuscript, we demonstrate that 4.2-kb of the 5′-flanking region of the UT-A gene (UT-Aα promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, β-galactosidase (β-Gal), in transgenic mice. RT-PCR, immunoblotting and immunohistochemistry demonstrate that within the kidney, transgene expression is confined to the terminal portion of the IMCD. Co-localization studies with aquaporin 2 show that expression is localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing β-Gal activity assays, we further show that within the kidney, the β-Gal transgene can be regulated by both water restriction and glucocorticoids, similar to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2-kb of the UT-Aα promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice