ArticleJournal of the American Society of Nephrology : JASN2016
Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Physiological Functions of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Tissue Distribution, Expression and Regulation of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Preclinical Pharmacokinetic Studies of a Novel Diuretic Inhibiting Urea Transporters.Molecules (Basel, Switzerland) · 2022Article
- Discovery of novel diarylamides as orally active diuretics targeting urea transporters.Acta pharmaceutica Sinica. B · 2021Article
- Water transport mediated by murine urea transporters: implications for urine concentration mechanisms.Biology open · 2020Article
- The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism.The Journal of biological chemistry · 2020Article
- Inhibition of urea transporter ameliorates uremic cardiomyopathy in chronic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- UT-A1/A3 knockout mice show reduced fibrosis following unilateral ureteral obstruction.American journal of physiology. Renal physiology · 2020Article
- Lack of urea transporters, UT-A1 and UT-A3, increases nitric oxide accumulation to dampen medullary sodium reabsorption through ENaC.American journal of physiology. Renal physiology · 2019Article
- Urinary concentrating defect in mice lacking Epac1 or Epac2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Mammalian urine concentration: a review of renal medullary architecture and membrane transporters.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2018Review
- Nanomolar-Potency 1,2,4-Triazoloquinoxaline Inhibitors of the Kidney Urea Transporter UT-A1.Journal of medicinal chemistry · 2018Article
- Generation and phenotypic analysis of mice lacking all urea transporters.Kidney international · 2017Article
- Urea transport and clinical potential of urearetics.Current opinion in nephrology and hypertension · 2016Review
- Modulation of kidney urea transporter UT-A3 activity by alpha2,6-sialylation.Pflugers Archiv : European journal of physiology · 2016Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1(+/+)/UT-A3(-/-)). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1(+/+)/UT-A3(-/-) and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1(+/+)/UT-A3(-/-) and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1(+/+)/UT-A3(-/-) mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1(+/+)/UT-A3(-/-) mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1(+/+)/UT-A3(-/-) mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1(+/+)/UT-A3(-/-) mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability.
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