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Am J Physiol Renal Physiol (August 9, 2005). doi:10.1152/ajprenal.00285.2005
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Submitted on July 12, 2005
Accepted on July 31, 2005

The UT-A Urea Transporter Promoter, UT-A{alpha}, Targets Principal Cells of the Renal Inner Medullary Collecting Duct

Robert A. Fenton1*, Adetola Shodeinde1, and Mark A. Knepper1

1 Laboratory of Kidney and Electrolyte Metabolism, National Institutes of Health, Bethesda, MD, USA

* To whom correspondence should be addressed. E-mail: ROFE{at}ana.au.dk.

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-A{alpha} promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, {beta}-galactosidase ({beta}-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 {beta}-Gal activity assays, we further show that within the kidney, the {beta}-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-A{alpha} promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice.







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