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Gene Review

Aqp3  -  aquaporin 3

Mus musculus

Synonyms: AQP-3, Aquaglyceroporin-3, Aquaporin-3
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Disease relevance of Aqp3

  • The renal medulla in most AQP1/AQP3 null mice by age 4 weeks was atrophic and fluid-filled due to the severe polyuria and hydronephrosis [1].
  • Modulation of AQP3 expression or function may thus alter epidermal moisture content and water loss in skin diseases [2].
  • RESULTS: The present study confirms that AQP3 null mice exhibit severe polyuria and polydipsia and demonstrated that they exhibit increased urinary sodium excretion [3].
  • Although more discrete, AQP-3 immunolabeling was also increased by dehydration [4].
  • In contrast, there was judged qualitatively to be a reduction in the amounts of AQP-2 and AQP-3 expression, especially in lesions with substantial interstitial fibrosis and nephron loss, as compared with a healthy region of normal kidneys [5].

Psychiatry related information on Aqp3

  • Mice lacking AQP3, a basolateral membrane water channel expressed mainly in the cortical collecting duct, are remarkably polyuric but are able to generate a partly concentrated urine after water deprivation [6].

High impact information on Aqp3

  • Analysis of [14C]glycerol kinetics indicated reduced blood-to-SC transport of glycerol in AQP3 null mice, resulting in slowed lipid biosynthesis [7].
  • Orally administered glycerol fully corrected the reduced skin elasticity in AQP3 null mice as measured by the kinetics of skin displacement after suction, and the delayed barrier recovery as measured by transepidermal water loss after tape-stripping [7].
  • Abundant AQP3 expression was seen in basal levels of epidermis, but not in sweat glands [8].
  • Aquaporin-3 (AQP3) is a water channel expressed at the basolateral plasma membrane of kidney collecting-duct epithelial cells [9].
  • After 1-desamino-8-d-arginine-vasopressin administration or water deprivation, the AQP3 null mice were able to concentrate their urine partially to approximately 30% of that in wild-type mice [9].

Biological context of Aqp3


Anatomical context of Aqp3

  • Here AQP1/AQP3 double knockout mice were generated and analyzed to investigate the functional role of AQP3 in erythrocytes and kidneys [1].
  • In blastocysts, AQP 3 and 8 were detected in the basolateral membrane domains of the trophectoderm, while AQP3 was also observed in cell margins of all inner cell mass (ICM) cells [13].
  • AQP 3, 8, and 9 proteins demonstrated cell margin-associated staining starting at the 8-cell (AQP 9) or compacted morula (AQP 3 and 8) stages [13].
  • In addition, aquaporin 3 expression was downregulated at the transcriptional level and glycerol uptake was reduced upon primary mouse keratinocytes to differentiation in response to an elevated extracellular calcium concentration or 1,25-dihydroxyvitamin D3 [10].
  • We report here that AQP3, AQP7 and AQP9 were expressed in the inner ear [14].

Associations of Aqp3 with chemical compounds

  • Our data provide direct evidence that AQP3 is not functionally important in erythrocyte water or glycerol permeability [1].
  • Polarized trafficking of the aquaporin-3 water channel is mediated by an NH2-terminal sorting signal [15].
  • A potential sorting signal consisting of tyrosine- and dileucine-based motifs was subsequently identified in the AQP3 NH2 terminus [15].
  • This solute-selective response could result from the capacity of AQP3 to transport not only water but also urea [11].
  • The SC content of ions (Na(+), K(+), Ca(2+), Mg(2+)) and small solutes (urea, lactic acid, glucose) was not affected by AQP3 deletion nor was the absolute amount or profile of lipids and free amino acids [16].

Regulatory relationships of Aqp3


Other interactions of Aqp3


Analytical, diagnostic and therapeutic context of Aqp3

  • Upper airway humidification, measured from the moisture gained by dry air passed through the upper airways in mice breathing through a tracheotomy, decreased from 91 to 50% with increasing ventilation from 20 to 220 ml/min, and reduced by 3-5% in AQP3/AQP4 knockout mice [19].
  • By electron microscopy AQP3 deletion did not affect the structure of the unperturbed SC [16].
  • Messenger RNA profiling (real-time RT-PCR) revealed changes in UT-A1, beta-ENaC, gamma-ENaC, and AQP3 transcript abundance that paralleled the changes in protein abundance [20].
  • By in situ hybridization and immunohistochemistry, AQP3 was preferentially expressed in basal cell layers of the cervical epithelium, whereas AQP4, 5, and 8 were primarily expressed in apical cell layers [12].
  • AQP1, AQP3, and AQP5 protein were confirmed in these tissues by immunoblotting [8].


  1. Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3. Yang, B., Ma, T., Verkman, A.S. J. Biol. Chem. (2001) [Pubmed]
  2. Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3. Ma, T., Hara, M., Sougrat, R., Verbavatz, J.M., Verkman, A.S. J. Biol. Chem. (2002) [Pubmed]
  3. Decreased expression of AQP2 and AQP4 water channels and Na,K-ATPase in kidney collecting duct in AQP3 null mice. Kim, S.W., Gresz, V., Rojek, A., Wang, W., Verkman, A.S., Frøkiaer, J., Nielsen, S. Biol. Cell (2005) [Pubmed]
  4. Phenotypic flexibility at the molecular and organismal level allows desert-dwelling rodents to cope with seasonal water availability. Gallardo, P.A., Cortes, A., Bozinovic, F. Physiol. Biochem. Zool. (2005) [Pubmed]
  5. Aquaporin expression in normal human kidney and in renal disease. Bedford, J.J., Leader, J.P., Walker, R.J. J. Am. Soc. Nephrol. (2003) [Pubmed]
  6. Physiological importance of aquaporins: lessons from knockout mice. Verkman, A.S. Curr. Opin. Nephrol. Hypertens. (2000) [Pubmed]
  7. Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Hara, M., Verkman, A.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Functional requirement of aquaporin-5 in plasma membranes of sweat glands. Nejsum, L.N., Kwon, T.H., Jensen, U.B., Fumagalli, O., Frøkiaer, J., Krane, C.M., Menon, A.G., King, L.S., Agre, P.C., Nielsen, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Ma, T., Song, Y., Yang, B., Gillespie, A., Carlson, E.J., Epstein, C.J., Verkman, A.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation. Zheng, X., Bollinger Bollag, W. J. Invest. Dermatol. (2003) [Pubmed]
  11. Urea and urine concentrating ability in mice lacking AQP1 and AQP3. Zhao, D., Bankir, L., Qian, L., Yang, D., Yang, B. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  12. Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening. Anderson, J., Brown, N., Mahendroo, M.S., Reese, J. Endocrinology (2006) [Pubmed]
  13. Aquaporin proteins in murine trophectoderm mediate transepithelial water movements during cavitation. Barcroft, L.C., Offenberg, H., Thomsen, P., Watson, A.J. Dev. Biol. (2003) [Pubmed]
  14. Expression patterns of aquaporins in the inner ear: evidence for concerted actions of multiple types of aquaporins to facilitate water transport in the cochlea. Huang, D., Chen, P., Chen, S., Nagura, M., Lim, D.J., Lin, X. Hear. Res. (2002) [Pubmed]
  15. Polarized trafficking of the aquaporin-3 water channel is mediated by an NH2-terminal sorting signal. Rai, T., Sasaki, S., Uchida, S. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  16. Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery. Hara, M., Ma, T., Verkman, A.S. J. Biol. Chem. (2002) [Pubmed]
  17. Developmental expression of urine concentration-associated genes and their altered expression in murine infantile-type polycystic kidney disease. Gattone, V.H., Maser, R.L., Tian, C., Rosenberg, J.M., Branden, M.G. Dev. Genet. (1999) [Pubmed]
  18. Estrogen regulation of aquaporins in the mouse uterus: potential roles in uterine water movement. Jablonski, E.M., McConnell, N.A., Hughes, F.M., Huet-Hudson, Y.M. Biol. Reprod. (2003) [Pubmed]
  19. Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration. Song, Y., Jayaraman, S., Yang, B., Matthay, M.A., Verkman, A.S. J. Gen. Physiol. (2001) [Pubmed]
  20. Altered expression profile of transporters in the inner medullary collecting duct of aquaporin-1 knockout mice. Morris, R.G., Uchida, S., Brooks, H., Knepper, M.A., Chou, C.L. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
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