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Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice

Item Type:Article
Title:Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice
Creators Name:Bachmann, S. and Mutig, K. and Bates, J. and Welker, P. and Geist, B. and Gross, V. and Luft, F.C. and Alenina, N. and Bader, M. and Thiele, B.J. and Prasadan, K. and Raffi, H.S. and Kumar, S.
Abstract:The Tamm-Horsfall protein (THP; uromodulin), the dominant protein in normal urine, is produced exclusively in the thick ascending limb of Henle's loop. THP mutations are associated with disease; however, the physiological role of THP remains obscure. We generated THP gene-deficient mice (THP -/-) and compared them with wild-type (WT) mice. THP -/-mice displayed anatomically normal kidneys. Steady-state electrolyte handling was not different between strains. Creatinine clearance was 63% lower in THP -/- than in WT mice (P < 0.05). Sucrose loading induced no changes between strains. However, water deprivation for 24 h decreased urine volume from 58 ± 9 to 28 ± 4 μl·g body wt-1·24 h-1 in WT mice (P < 0.05), whereas in THP -/- mice this decrease was less pronounced (57 ± 4 to 41 ± 5 μl·g body wt-1·24 h-1; P < 0.05), revealing significant interstrain difference (P < 0.05). We further used RT-PCR, Northern and Western blotting, and histochemistry to study renal transporters, channels, and regulatory systems under steady-state conditions. We found that major distal transporters were upregulated in THP -/- mice, whereas juxtaglomerular immunoreactive cyclooxygenase-2 (COX-2) and renin mRNA expression were both decreased in THP -/- compared with WT mice. These observations suggest that THP influences transporters in Henle's loop. The decreased COX-2 and renin levels may be related to an altered tubular salt load at the macula densa, whereas the increased expression of distal transporters may reflect compensatory mechanisms. Our data raise the hypothesis that THP plays an important regulatory role in the kidney.
Keywords:Gene-Disrupted Mice, Renal Concentrating Mechanism, Thick ascending limb, Animals, Mice
Source:American Journal of Physiology Renal Physiology
ISSN:0363-6127
Publisher:American Physiological Society (U.S.A.)
Volume:288
Number:3
Page Range:F559-F567
Date:1 January 2005
Official Publication:https://doi.org/10.1152/ajprenal.00143.2004
PubMed:View item in PubMed

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