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PMID:11792714
Citation |
Yang, B, Bankir, L, Gillespie, A, Epstein, CJ and Verkman, AS (2002) Urea-selective concentrating defect in transgenic mice lacking urea transporter UT-B. J. Biol. Chem. 277:10633-7 |
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Abstract |
Urea transporter UT-B has been proposed to be the major urea transporter in erythrocytes and kidney-descending vasa recta. The mouse UT-B cDNA was isolated and encodes a 384-amino acid urea-transporting glycoprotein expressed in kidney, spleen, brain, ureter, and urinary bladder. The mouse UT-B gene was analyzed, and UT-B knockout mice were generated by targeted gene deletion of exons 3-6. The survival and growth of UT-B knockout mice were not different from wild-type littermates. Urea permeability was 45-fold lower in erythrocytes from knockout mice than from those in wild-type mice. Daily urine output was 1.5-fold greater in UT-B- deficient mice (p < 0.01), and urine osmolality (U(osm)) was lower (1532 +/- 71 versus 2056 +/- 83 mosM/kg H(2)O, mean +/- S.E., p < 0.001). After 24 h of water deprivation, U(osm) (in mosM/kg H(2)O) was 2403 +/- 38 in UT-B null mice and 3438 +/- 98 in wild-type mice (p < 0.001). Plasma urea concentration (P(urea)) was 30% higher, and urine urea concentration (U(urea)) was 35% lower in knockout mice than in wild-type mice, resulting in a much lower U(urea)/P(urea) ratio (61 +/- 5 versus 124 +/- 9, p < 0.001). Thus, the capacity to concentrate urea in the urine is more severely impaired than the capacity to concentrate other solutes. Together with data showing a disproportionate reduction in the concentration of urea compared with salt in homogenized renal inner medullas of UT-B null mice, these data define a novel "urea-selective" urinary concentrating defect in UT-B null mice. The UT-B null mice generated for these studies should also be useful in establishing the role of facilitated urea transport in extrarenal organs expressing UT-B. |
Links |
PubMed Online version:10.1074/jbc.M200207200 |
Keywords |
Amino Acid Sequence; Animals; Blotting, Northern; Carrier Proteins/genetics; Carrier Proteins/physiology; Cloning, Molecular; DNA, Complementary/metabolism; Dose-Response Relationship, Drug; Erythrocytes/metabolism; Exons; Immunoblotting; Immunohistochemistry; Kidney Concentrating Ability; Membrane Glycoproteins/genetics; Membrane Glycoproteins/physiology; Membrane Transport Proteins/biosynthesis; Membrane Transport Proteins/chemistry; Membrane Transport Proteins/physiology; Mice; Mice, Transgenic; Models, Biological; Models, Genetic; Molecular Sequence Data; Phenotype; Sequence Homology, Amino Acid; Time Factors; Tissue Distribution; Urea/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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