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Molecular and Cellular Biology, August 2005, p. 7357-7363, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7357-7363.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Impaired Urea Accumulation in the Inner Medulla of Mice Lacking the Urea Transporter UT-A2

Shinichi Uchida,1* Eisei Sohara,1 Tatemitsu Rai,1 Masahito Ikawa,2 Masaru Okabe,2 and Sei Sasaki1

Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo,1 Genome Information Research Center, Osaka University, Osaka, Japan2

Received 31 January 2005/ Returned for modification 21 April 2005/ Accepted 31 May 2005

Urea transporter UT-A2, the major urea transporter of the thin descending limb of the loop of Henle in short loop nephrons, has been implicated in urea recycling in the medulla, thereby producing concentrated urine. To investigate the physiological role of UT-A2 in vivo, we generated UT-A2-selective knockout mice by deleting the UT-A2 promoter. Western analysis, immunohistochemistry, and quantitative reverse transcription-PCR were used to confirm the specific deletion of UT-A2 with preservation of other UT-A transporters. Compared to wild-type mice, differences in the urine outputs of UT-A2–/– mice consuming a normal protein diet (20% protein) were not observed under normal conditions or with dehydration. Likewise, impairment of urea accumulation in the inner medulla of UT-A2–/– mice was not observed. On a low-protein diet (4% protein), however, significantly reduced maximal urine osmolality was observed in dehydrated UT-A2–/– mice compared to wild-type littermates (2,500 mosmol versus 3,450 mosmol, respectively). A significant reduction in urea accumulation in the inner medulla was also observed in UT-A2–/– mice; however, differences in Na+ and Cl– accumulation were not observed. Thus, UT-A2 is important for maintaining a high concentration of urea in the inner medulla when urea supply to the kidney is limited.

* Corresponding author. Mailing address: 1-5-45 Yushima Bunkyo, Tokyo 113-8519, Japan. Phone: 81-3-5803-5214. Fax: 81-3-5803-5215. E-mail: suchida.kid{at}tmd.ac.jp.

Molecular and Cellular Biology, August 2005, p. 7357-7363, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.7357-7363.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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