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Am J Physiol Renal Physiol 290: F188-F195, 2006. First published August 9, 2005; doi:10.1152/ajprenal.00285.2005
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UT-A urea transporter promoter, UT-A{alpha}, targets principal cells of the renal inner medullary collecting duct

Robert A. Fenton, Adetola Shodeinde, and Mark A. Knepper

Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

Submitted 12 July 2005 ; accepted in final form 31 July 2005

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. Colocalization 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.

transgenic; kidney; {beta}-galactosidase


Address for reprint requests and other correspondence: R. A. Fenton, The Water and Salt Research Center, Institute of Anatomy, Bldg. 233/234, Univ. of Aarhus, DK-8000, Aarhus, Denmark (e-mail: ROFE{at}ana.au.dk)






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