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Publication : Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2.

First Author  Uchida S Year  2005
Journal  Mol Cell Biol Volume  25
Issue  16 Pages  7357-63
PubMed ID  16055743 Mgi Jnum  J:119860
Mgi Id  MGI:3703389 Doi  10.1128/MCB.25.16.7357-7363.2005
Citation  Uchida S, et al. (2005) Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2. Mol Cell Biol 25(16):7357-63
abstractText  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.
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