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J. Biol. Chem., Vol. 277, Issue 12, 10633-10637, March 22, 2002
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From the Departments of 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
(Uosm) was lower (1532 ± 71 versus 2056 ± 83 mosM/kgH2O,
mean ± S.E., p < 0.001). After 24 h of
water deprivation, Uosm (in
mosM/kgH2O) was 2403 ± 38 in UT-B null
mice and 3438 ± 98 in wild-type mice (p < 0.001). Plasma urea concentration (Purea) was
30% higher, and urine urea concentration
(Uurea) was 35% lower in knockout mice than in
wild-type mice, resulting in a much lower
Uurea/Purea 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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF448798.
Urea-selective Concentrating Defect in Transgenic Mice Lacking
Urea Transporter UT-B*
§,¶,
,, and
Medicine and Physiology and
Pediatrics, Cardiovascular Research Institute, University of
California, San Francisco, California 94143-0521 and ¶ INSERM Unit
367, Institut du Fer a Moulin, 75005 Paris, France
*
This work was supported in part by National Institutes of
Health Grants HL58198, DK35124, HL60288, and HL51854 and Grant R613 from the National Cystic Fibrosis Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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