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Gene Review

Umod  -  uromodulin

Mus musculus

Synonyms: THP, Tamm-Horsfall glycoprotein, Tamm-Horsfall urinary glycoprotein, Urehd1, Uromodulin, ...
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Disease relevance of Umod

  • We show that renal cyst formation is accompanied by a drastic defect in the transcriptional activation of Umod, Pkhd1 and Pkd2 genes, whose mutations are responsible for distinct cystic kidney syndromes [1].
  • Downregulation of EGF could potentially affect renal development, and THP/uromodulin gene has been implicated in abnormal kidney development and end-stage renal failure in humans [2].
  • In contrast, THP deficiency did not enhance the ability of P-fimbriated E. coli to colonize the bladder [3].
  • These results suggest that potential THP defects, either quantitative or qualitative, could predispose the urinary bladder to bacterial infections [3].
  • CONCLUSION: These results provide the first in vivo evidence that THP is a critical urinary defense factor and suggest that its deficiency could be an important contributing factor in human nephrolithiasis, a condition afflicting tens of millions of people in the world annually [4].

Psychiatry related information on Umod

  • However, water deprivation for 24 h decreased urine volume from 58 +/- 9 to 28 +/- 4 microl x g body wt(-1) x 24 h(-1) in WT mice (P < 0.05), whereas in THP -/- mice this decrease was less pronounced (57 +/- 4 to 41 +/- 5 microl x g body wt(-1) x 24 h(-1); P < 0.05), revealing significant interstrain difference (P < 0.05) [5].

High impact information on Umod

  • These data show that THP is a regulatory factor of innate and adaptive immunity and therefore could have significant impact on host immunity in the urinary tract [6].
  • A critical role for THP in antibacterial host defense and inflammatory disorders of the urogenital tract has been suggested [6].
  • It competitively inhibited the binding capacity of MS pili and was found to be physically, chemically, and immunologically related to Tamm-Horsfall uromucoid [7].
  • Specific gene expression profiles were obtained, and known markers (e.g., uromodulin in the thick ascending limb of Henle's loop and aquaporin-2 in the collecting duct) were found appropriately enriched [8].
  • Tamm-Horsfall glycoprotein (THGP) and the oligosaccharide fraction liberated from THGP by hydrazinolysis inhibited tetanus toxoid-induced T cell proliferation [9].

Chemical compound and disease context of Umod


Biological context of Umod


Anatomical context of Umod

  • Defective expression of Tamm-Horsfall protein/uromodulin in COX-2-deficient mice increases their susceptibility to urinary tract infections [2].
  • RESULTS: Inactivating the THP gene in mouse embryonic stem cells results in spontaneous formation of calcium crystals in adult kidneys [4].
  • THP mRNA expression was detected only in kidney, whereas CreTag mRNA was also present in testes [16].
  • As we have shown in rats, THP withdrawal also resulted in increased expression of the alpha4 subunit in mouse CA1 hippocampus [17].
  • Cortex, olfactory bulb and hypothalamus synthesized levels of DHP were significantly raised after 9 days of paroxetine administration, whereas a significant rise in the THP synthesized level was observed only after 21 days of treatment [18].

Associations of Umod with chemical compounds

  • Creatinine clearance was 63% lower in THP -/- than in WT mice (P < 0.05) [5].
  • The segmental localization of vasopressin-receptor mRNAs was determined using simultaneous in situ hybridization and immunohistochemistry for segment-specific markers, including aquaporin-2, Dolichos biflorus agglutinin, epithelial Na channels, Tamm Horsfall glycoprotein, and thiazide-sensitive Na(+)-Cl(-) cotransporter [19].
  • Our results establish the kidney- and nephron-segment-specific expression of the mouse THP gene [14].
  • Excessive intake of calcium and oxalate, precursors of the most common type of human renal stones, dramatically increases both the frequency and the severity of renal calcium crystal formation in THP-deficient, but not in wild-type mice [4].
  • The polypeptide of uromodulin, an immunosuppressive glycoprotein isolated from human urine, has been shown to be identical to that of Tamm-Horsfall glycoprotein and is synthesized exclusively in the kidney (Hession, C., Decker, J [20].

Physical interactions of Umod

  • Our results provide the first in vivo evidence indicating that under physiological conditions, the mannosylated THP can serve as an effective soluble "receptor," binding to the type 1-fimbriated E. coli and competitively inhibiting them from adhering to the uroplakin Ia receptors present on the urothelial surface [3].

Other interactions of Umod

  • The present study evaluated the expression of four relatively well-localized molecules--renin, Tamm-Horsfall protein (THP), oxytocin receptor (OTR), and the vasopressin type 2 receptor (V2R)--in cultured mouse-rat chimeric metanephric kidneys using reverse transcription-polymerase chain reaction (RT-PCR) [21].
  • Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a toll-like receptor-4-dependent mechanism [22].

Analytical, diagnostic and therapeutic context of Umod

  • The availability of the mouse THP gene promoter that functions in vivo should facilitate additional studies of the molecular mechanisms of kidney-specific gene regulation and should provide new molecular tools for better understanding renal physiology and disease through nephron-specific gene targeting [14].
  • Thus, OPN may serve as an inducible inhibitor of calcium crystallization, whereas THP can serve as a constitutive and apparently more effective inhibitor [4].
  • Assignment of the Tamm-Horsfall protein/uromodulin gene (Umod) to mouse chromosome bands 7F1-F2 and rat chromosome bands 1q36-->q37 by in situ hybridization [23].
  • These results indicate that the 3.0 kb mouse THP promoter is primarily kidney-specific and can be used to convert kidney into a bioreactor in transgenic animals to produce recombinant proteins [24].
  • After intravenous injection of L-THP, the accumulations of THP in the liver and heart were approximately 4-fold higher and half lower, respectively, than those of free THP (F-THP) [12].


  1. A transcriptional network in polycystic kidney disease. Gresh, L., Fischer, E., Reimann, A., Tanguy, M., Garbay, S., Shao, X., Hiesberger, T., Fiette, L., Igarashi, P., Yaniv, M., Pontoglio, M. EMBO J. (2004) [Pubmed]
  2. Defective expression of Tamm-Horsfall protein/uromodulin in COX-2-deficient mice increases their susceptibility to urinary tract infections. Dou, W., Thompson-Jaeger, S., Laulederkind, S.J., Becker, J.W., Montgomery, J., Ruiz-Bustos, E., Hasty, D.L., Ballou, L.R., Eastman, P.S., Srichai, B., Breyer, M.D., Raghow, R. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  3. Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli. Mo, L., Zhu, X.H., Huang, H.Y., Shapiro, E., Hasty, D.L., Wu, X.R. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  4. Tamm-Horsfall protein is a critical renal defense factor protecting against calcium oxalate crystal formation. Mo, L., Huang, H.Y., Zhu, X.H., Shapiro, E., Hasty, D.L., Wu, X.R. Kidney Int. (2004) [Pubmed]
  5. Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice. Bachmann, S., Mutig, K., Bates, J., Welker, P., Geist, B., Gross, V., Luft, F.C., Alenina, N., Bader, M., Thiele, B.J., Prasadan, K., Raffi, H.S., Kumar, S. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  6. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism. Säemann, M.D., Weichhart, T., Zeyda, M., Staffler, G., Schunn, M., Stuhlmeier, K.M., Sobanov, Y., Stulnig, T.M., Akira, S., von Gabain, A., von Ahsen, U., Hörl, W.H., Zlabinger, G.J. J. Clin. Invest. (2005) [Pubmed]
  7. Molecular basis of Escherichia coli colonization of the upper urinary tract in BALB/c mice. Gal-Gal pili immunization prevents Escherichia coli pyelonephritis in the BALB/c mouse model of human pyelonephritis. O'Hanley, P., Lark, D., Falkow, S., Schoolnik, G. J. Clin. Invest. (1985) [Pubmed]
  8. Serial microanalysis of renal transcriptomes. Virlon, B., Cheval, L., Buhler, J.M., Billon, E., Doucet, A., Elalouf, J.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Detection of novel carbohydrate binding activity of interleukin-1. Tandai-Hiruma, M., Endo, T., Kobata, A. J. Biol. Chem. (1999) [Pubmed]
  10. Adenosinergic modulation of 3alpha-hydroxy-5alpha-pregnan-20-one induced catalepsy in mice. Mandhane, S.N., Khisti, R.T., Chopde, C.T. Psychopharmacology (Berl.) (1999) [Pubmed]
  11. Laser flow cytometric studies on the intracellular accumulation of anthracyclines when combined with heat. Sakaguchi, Y., Maehara, Y., Inutsuka, S., Takahashi, I., Yoshida, M., Emi, Y., Baba, H., Sugimachi, K. Cancer Chemother. Pharmacol. (1994) [Pubmed]
  12. Preparation and pharmacokinetics of pirarubicin loaded dehydration-rehydration vesicles. Kawano, K., Takayama, K., Nagai, T., Maitani, Y. International journal of pharmaceutics. (2003) [Pubmed]
  13. Influence of chlorpromazine on the toxicity of pirarubicin in mice. Maekawa, I., Shibata, H., Furusawa, S., Takayanagi, Y., Sasaki, K. Res. Commun. Chem. Pathol. Pharmacol. (1991) [Pubmed]
  14. Isolation of mouse THP gene promoter and demonstration of its kidney-specific activity in transgenic mice. Zhu, X., Cheng, J., Gao, J., Lepor, H., Zhang, Z.T., Pak, J., Wu, X.R. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  15. GP2/THP gene family of self-binding, GPI-anchored proteins forms a cluster at chromosome 7F1 region in mouse genome. Kobayashi, K., Yanagihara, K., Ishiguro, K., Fukuoka, S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  16. Thick ascending limb-specific expression of Cre recombinase. Stricklett, P.K., Taylor, D., Nelson, R.D., Kohan, D.E. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  17. Steroid withdrawal in the mouse results in anxiogenic effects of 3alpha,5beta-THP: a possible model of premenstrual dysphoric disorder. Smith, S.S., Ruderman, Y., Frye, C., Homanics, G., Yuan, M. Psychopharmacology (Berl.) (2006) [Pubmed]
  18. Brain neurosteroid changes after paroxetine administration in mice. Nechmad, A., Maayan, R., Spivak, B., Ramadan, E., Poyurovsky, M., Weizman, A. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2003) [Pubmed]
  19. Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct. Carmosino, M., Brooks, H.L., Cai, Q., Davis, L.S., Opalenik, S., Hao, C., Breyer, M.D. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  20. The lectin-like interaction between recombinant tumor necrosis factor and uromodulin. Sherblom, A.P., Decker, J.M., Muchmore, A.V. J. Biol. Chem. (1988) [Pubmed]
  21. Metanephric rat-mouse chimeras to study cell lineage of the nephron. Arend, L.J., Smart, A., Briggs, J.P. Dev. Genet. (1999) [Pubmed]
  22. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a toll-like receptor-4-dependent mechanism. Ratliff, T.L. J. Urol. (2005) [Pubmed]
  23. Assignment of the Tamm-Horsfall protein/uromodulin gene (Umod) to mouse chromosome bands 7F1-F2 and rat chromosome bands 1q36-->q37 by in situ hybridization. Fukuoka, S., Matsuda, Y. Cytogenet. Cell Genet. (1997) [Pubmed]
  24. Renal tubule-specific expression and urinary secretion of human growth hormone: a kidney-based transgenic bioreactor growth. Zhu, X., Cheng, J., Huang, L., Gao, J., Zhang, Z.T., Pak, J., Wu, X.R. Transgenic Res. (2003) [Pubmed]
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