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Gene Review

Aqp5  -  aquaporin 5

Mus musculus

Synonyms: AQP-5, Aquaporin-5
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Disease relevance of Aqp5


High impact information on Aqp5

  • P(f) was reduced 10-fold by AQP5 deletion and was further reduced by 2- to 3-fold in AQP1/AQP5 double-knockout mice [2].
  • These results indicate that AQP5 is responsible for the majority of water transport across the apical membrane of type I alveolar epithelial cells [2].
  • Interestingly, fluid absorption did not differ in litter-matched AQP5 knockout mice, nor was there an effect of AQP5 deletion when fluid absorption was maximally stimulated by pretreatment of mice with keratinocyte growth factor [2].
  • Distribution of salivary aquaporin-5 in Sjögren's syndrome [6].
  • Similarly, addition of hypotonic PBS to mouse trachea in vivo decreased AQP5 within 1 h, an effect blocked by ruthenium red [7].

Chemical compound and disease context of Aqp5


Biological context of Aqp5

  • Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5(-/-) mice challenged with aerosolized methacholine (P < 0.05) [10].
  • This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene [10].
  • Compared with Aqp5(+/+) mice, Aqp5(-/-) mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05) [10].
  • Here we show that the decreased salivary flow rate and increased tonicity of the saliva secreted by Aqp5(-)/- mice in response to pilocarpine stimulation are not caused by changes in whole body fluid homeostasis, indicated by similar blood gas and electrolyte concentrations in urine and blood in wild-type and AQP5-deficient mice [11].
  • The genotype distribution from intercross of founder AQP5 heterozygous mice was 70:69:29 wild-type:heterozygote:knockout, indicating impaired prenatal survival of the null mice [12].

Anatomical context of Aqp5

  • An Aqp5 antibody detects an approximately 27-kDa protein band in mouse lung, and an additional 29 kDa band in salivary gland [13].
  • Expression of aquaporin 1 and 5 in the developing mouse inner ear and audiovestibular assessment of an Aqp5 null mutant [14].
  • These results implicate a key role for AQP5 in saliva fluid secretion and provide direct evidence that high epithelial cell membrane water permeability is required for active, near-isosmolar fluid transport [12].
  • The antibody to the AQP5 carboxy terminus showed high immunoreactivity on the apical membrane in the pilocarpine-treated lacrimal glands but not on that of saline-treated controls [15].
  • AQP5 immunolabeling was detected in the apical membranes of the acinus and duct cells, while AQP4 was expressed in the basolateral membranes only [15].

Associations of Aqp5 with chemical compounds


Regulatory relationships of Aqp5


Other interactions of Aqp5

  • AQP5 and AQP8 expression were significantly increased on d 12-15 but fell to nongravid/baseline by d 19 and PP1 [22].
  • By immunohistochemistry, AQP5 is localized in the basolateral region of the uterine glands [23].
  • These findings demonstrate that LPS increases cell surface AQP5 expression by changing its subcellular distribution and increases membrane osmotic water permeability through activation of p38 MAP kinase [21].
  • In the absence of T1alpha protein, type I cell differentiation is blocked, as indicated by smaller airspaces, many fewer attenuated type I cells, and reduced levels of aquaporin-5 mRNA and protein, a type I cell water channel [24].
  • Aquaporin-5 expression, but not other peripheral lung marker genes, is reduced in PTH/PTHrP receptor null mutant fetal mice [25].

Analytical, diagnostic and therapeutic context of Aqp5

  • Standard in situ hybridization (ISH) and immunohistochemical (IHC) assays were used for expression studies with routine morphologic, behavioral, and physiologic assessments of hearing and balance in Aqp5 null mutant mice [14].
  • As shown by western blot analysis, the expression level of AQP5 on the apical membrane in the pilocarpine-stimulated lacrimal glands was not significantly different compared with the saline-treated controls [15].
  • By z-scanning confocal microscopy, corneal thickness in vivo was (in microm, mean +/- S.E., n = 5 mice) 123 +/- 1 (wild type), 101 +/- 2 (AQP1 null), and 144 +/- 2 (AQP5 null) [26].
  • Immunoblotting studies demonstrated significantly reduced levels of AQP1 and AQP5 protein after infection as well [27].
  • Northern blot analysis showed significantly decreased mRNA levels of AQP1, which is expressed in the capillary endothelium, and AQP5, which is expressed in alveolar epithelium, in the lungs of mice both 7 and 14 d after infection [27].


  1. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice. Song, Y., Fukuda, N., Bai, C., Ma, T., Matthay, M.A., Verkman, A.S. J. Physiol. (Lond.) (2000) [Pubmed]
  2. Lung fluid transport in aquaporin-5 knockout mice. Ma, T., Fukuda, N., Song, Y., Matthay, M.A., Verkman, A.S. J. Clin. Invest. (2000) [Pubmed]
  3. Aquaporin-5 dependent fluid secretion in airway submucosal glands. Song, Y., Verkman, A.S. J. Biol. Chem. (2001) [Pubmed]
  4. 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]
  5. Role of aquaporin water channels in eye function. Verkman, A.S. Exp. Eye Res. (2003) [Pubmed]
  6. Distribution of salivary aquaporin-5 in Sjögren's syndrome. Groneberg, D.A., Peiser, C., Fischer, A. Lancet (2002) [Pubmed]
  7. Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions. Sidhaye, V.K., Güler, A.D., Schweitzer, K.S., D'Alessio, F., Caterina, M.J., King, L.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Leakage of aquaporin 5 in the tear of dacryoadenitis mice. Hirai, S., Ishida, N., Watanabe, K., Mita, S. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  9. Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse. Gabazza, E.C., Kasper, M., Ohta, K., Keane, M., D'Alessandro-Gabazza, C., Fujimoto, H., Nishii, Y., Nakahara, H., Takagi, T., Menon, A.G., Adachi, Y., Suzuki, K., Taguchi, O. Pathol. Int. (2004) [Pubmed]
  10. Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation. Krane, C.M., Fortner, C.N., Hand, A.R., McGraw, D.W., Lorenz, J.N., Wert, S.E., Towne, J.E., Paul, R.J., Whitsett, J.A., Menon, A.G. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  11. Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane water permeability and altered cell volume regulation. Krane, C.M., Melvin, J.E., Nguyen, H.V., Richardson, L., Towne, J.E., Doetschman, T., Menon, A.G. J. Biol. Chem. (2001) [Pubmed]
  12. Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels. Ma, T., Song, Y., Gillespie, A., Carlson, E.J., Epstein, C.J., Verkman, A.S. J. Biol. Chem. (1999) [Pubmed]
  13. Cloning and characterization of murine Aqp5: evidence for a conserved aquaporin gene cluster. Krane, C.M., Towne, J.E., Menon, A.G. Mamm. Genome (1999) [Pubmed]
  14. Expression of aquaporin 1 and 5 in the developing mouse inner ear and audiovestibular assessment of an Aqp5 null mutant. Merves, M., Krane, C.M., Dou, H., Greinwald, J.H., Menon, A.G., Choo, D. J. Assoc. Res. Otolaryngol. (2003) [Pubmed]
  15. Immunolocalization of aquaporin homologs in mouse lacrimal glands. Ishida, N., Hirai, S.I., Mita, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  16. cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells. Sidhaye, V., Hoffert, J.D., King, L.S. J. Biol. Chem. (2005) [Pubmed]
  17. Cyclic AMP regulates aquaporin 5 expression at both transcriptional and post-transcriptional levels through a protein kinase A pathway. Yang, F., Kawedia, J.D., Menon, A.G. J. Biol. Chem. (2003) [Pubmed]
  18. Conditional expression of fibroblast growth factor-7 in the developing and mature lung. Tichelaar, J.W., Lu, W., Whitsett, J.A. J. Biol. Chem. (2000) [Pubmed]
  19. Hypertonic induction of aquaporin-5 expression through an ERK-dependent pathway. Hoffert, J.D., Leitch, V., Agre, P., King, L.S. J. Biol. Chem. (2000) [Pubmed]
  20. GATA6 regulates differentiation of distal lung epithelium. Yang, H., Lu, M.M., Zhang, L., Whitsett, J.A., Morrisey, E.E. Development (2002) [Pubmed]
  21. Lipopolysaccharide changes the subcellular distribution of aquaporin 5 and increases plasma membrane water permeability in mouse lung epithelial cells. Ohinata, A., Nagai, K., Nomura, J., Hashimoto, K., Hisatsune, A., Miyata, T., Isohama, Y. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. 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]
  23. Aquaporin water channel genes are differentially expressed and regulated by ovarian steroids during the periimplantation period in the mouse. Richard, C., Gao, J., Brown, N., Reese, J. Endocrinology (2003) [Pubmed]
  24. T1alpha, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth. Ramirez, M.I., Millien, G., Hinds, A., Cao, Y., Seldin, D.C., Williams, M.C. Dev. Biol. (2003) [Pubmed]
  25. Aquaporin-5 expression, but not other peripheral lung marker genes, is reduced in PTH/PTHrP receptor null mutant fetal mice. Ramirez, M.I., Chung, U.I., Williams, M.C. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  26. Aquaporin deletion in mice reduces corneal water permeability and delays restoration of transparency after swelling. Thiagarajah, J.R., Verkman, A.S. J. Biol. Chem. (2002) [Pubmed]
  27. Decreased expression of aquaporin (AQP)1 and AQP5 in mouse lung after acute viral infection. Towne, J.E., Harrod, K.S., Krane, C.M., Menon, A.G. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
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