期刊论文详细信息
BMC Nephrology
UT-B-deficient mice develop renal dysfunction and structural damage
Baoxue Yang3  Xuejian Zhao2  Jing Su2  Dan Zhao2  Tianluo Lei3  Yan Meng2  Lei Zhou1 
[1]Department of Pathology, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
[2]Prostate Diseases Prevention and Treatment Research Center, Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, China
[3]Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China
关键词: knock-out;    UT-B;    kidney;    renal function;    urea transporter;   
Others  :  1083207
DOI  :  10.1186/1471-2369-13-6
 received in 2011-04-29, accepted in 2012-01-30,  发布年份 2012
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【 摘 要 】

Background

Urea transporter UT-B is the major urea transporter in erythrocytes and the descending vasa recta in the kidney. In this study, we investigated the effects of long-term UT-B deficiency on functional and structural defect in the kidney of 16-and 52-week-old UT-B-null mice.

Methods

UT-B-knockout mice were generated by targeted gene disruption and lacked UT-B protein expression in all organs. The urinary concentrating ability of mice was studied in terms of daily urine output, urine osmolality, and urine and plasma chemistries. Changes in renal morphology were evaluated by hematoxylin and eosin staining.

Results

The UT-B-null mice showed defective urine concentrating ability. The daily urine output in UT-B-null mice (2.5 ± 0.1 ml) was 60% higher and urine osmolality (985 ± 151 mosm) was significantly lower than that in wild-type mice (1463 ± 227 mosm). The 52-week-old UT-B-null mice exhibited polyuria after water deprivation, although urine osmolality was increased. At 52 weeks of age, over 31% of UT-B-null mice exhibited renal medullary atrophy because of severe polyuria and hydronephrosis.

Conclusions

Long-term UT-B deficiency causes severe renal dysfunction and structural damage. These results demonstrate the important role of UT-B in countercurrent exchange and urine concentration.

【 授权许可】

   
2012 Zhou et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Bankir L, Bouby N, Trinh-Trang-Tan MM, Ahloulay M, Promeneur D: Direct and indirect cost of urea excretion. Kidney Int 1996, 49:1598-1607.
  • [2]Bankir L, Trinh-Trang-Tan MM: Urea and the kidney. 6th edition. Philadelphia, PA: Saunders; 2000.
  • [3]Bray GA, Scott-Preston A: The role of urea in the concentration of non-urea solutes by the kidney. Amsterdam: Excerpta Medica; 1970.
  • [4]Schmidt-Nielsen B, Robinson RR: Contribution of urea to urinary concentrating ability in the dog. Am J Physiol 1970, 218:1363-1369.
  • [5]Xu Y, Olives B, Bailly P, Fischer E, Ripoche P, Ronco P, Cartron JP, Rondeau E: Endothelial cells of the kidney vasa recta express the urea transporter HUT11. Kidney Int 1997, 51:138-146.
  • [6]Lucien N, Sidoux-Walter F, Roudier N, Ripoche P, Huet M, Trinh-Trang-Tan MM, Cartron JP, Bailly P: Antigenic and functional properties of the human red blood cell urea transporter hUT-B1. J Biol Chem 2002, 277:34101-34108.
  • [7]Olives B, Mattei MG, Huet M, Neau P, Martial S, Cartron JP, Bailly P: Kidd blood group and urea transport function of human erythrocytes are carried by the same protein. J Biol Chem 1995, 270:15607-15610.
  • [8]Issitt PD, Anstee DJ: The Kidd blood group system. 4th edition. Montgomery: Scientific Publications; 1998.
  • [9]Meng Y, Zhou X, Li Y, Zhao D, Liang S, Zhao X, Yang B: A novel mutation at the JK locus causing Jk null phenotype in a Chinese family. Sci China C Life Sci 2005, 48:636-640.
  • [10]Frohlich O, Macey RI, Edwards-Moulds J, Gargus JJ, Gunn RB: Urea transport deficiency in Jk(a-b-) erythrocytes. Am J Physiol 1991, 260:C778-783.
  • [11]Bankir L, Chen K, Yang B: Lack of UT-B in vasa recta and red blood cells prevents urea-induced improvement of urinary concentrating ability. Am J Physiol Renal Physiol 2004, 286:F144-151.
  • [12]Sands JM, Gargus JJ, Frohlich O, Gunn RB, Kokko JP: Urinary concentrating ability in patients with Jk(a-b-) blood type who lack carrier-mediated urea transport. J Am Soc Nephrol 1992, 2:1689-1696.
  • [13]Yang B, Bankir L, Gillespie A, Epstein CJ, Verkman AS: Urea-selective concentrating defect in transgenic mice lacking urea transporter UT-B. J Biol Chem 2002, 277:10633-10637.
  • [14]Yang B, Bankir L: Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol 2005, 288:F881-896.
  • [15]Yang B, Ma T, Verkman AS: Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3. J Biol Chem 2001, 276:624-628.
  • [16]Uchida S, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S: Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2. Mol Cell Biol 2005, 25:7357-7363.
  • [17]Meng Y, Zhang XX, Zhao HS, Guo LR, Lu B, Zhao CY, Zhao XJ, Yang BX: Surface electrocardiogram and action potential in mice lacking urea transporter UT-B. Science in China Series C: Life Sciences 2007, 37:447-451.
  • [18]Yang B, Zhao D, Qian L, Verkman AS: Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion. Am J Physiol Renal Physiol 2006, 291:F465-472.
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