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J Biol Chem, Vol. 273, Issue 8, 4296-4299, February 20, 1998
From the Departments of Medicine, Physiology, and Pediatrics,
Cardiovascular Research Institute, University of California, San
Francisco, California 94143-0521
Water channel aquaporin-1 (AQP1) is strongly
expressed in kidney in proximal tubule and descending limb of Henle
epithelia and in vasa recta endothelia. The grossly normal phenotype in human subjects deficient in AQP1 (Colton null blood group) and in AQP4
knockout mice has suggested that aquaporins (other than the
vasopressin-regulated water channel AQP2) may not be important in
mammalian physiology. We have generated transgenic mice lacking detectable AQP1 by targeted gene disruption. In kidney proximal tubule
membrane vesicles from knockout mice, osmotic water permeability was
reduced 8-fold compared with vesicles from wild-type mice. Although the
knockout mice were grossly normal in terms of survival, physical
appearance, and organ morphology, they became severely dehydrated and
lethargic after water deprivation for 36 h. Body weight decreased
by 35 ± 2%, serum osmolality increased to >500 mOsm, and
urinary osmolality (657 ± 59 mOsm) did not change from that
before water deprivation. In contrast, wild-type and heterozygous mice
remained active after water deprivation, body weight decreased by
20-22%, serum osmolality remained normal (310-330 mOsm), and urine
osmolality rose to >2500 mOsm. Urine [Na+] in
water-deprived knockout mice was <10 mM, and urine
osmolality was not increased by the V2 agonist DDAVP. The results
suggest that AQP1 knockout mice are unable to create a hypertonic
medullary interstitium by countercurrent multiplication. AQP1 is thus
required for the formation of a concentrated urine by the kidney.
COMMUNICATION
Severely Impaired Urinary Concentrating Ability in Transgenic
Mice Lacking Aquaporin-1 Water Channels
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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C. Li, W. Wang, T.-H. Kwon, L. Isikay, J. G. Wen, D. Marples, J. C. Djurhuus, A. Stockwell, M. A. Knepper, S. Nielsen, et al. Downregulation of AQP1, -2, and -3 after ureteral obstruction is associated with a long-term urine-concentrating defect Am J Physiol Renal Physiol, July 1, 2001; 281(1): F163 - F171. [Abstract] [Full Text] [PDF]
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S.-W. KIM, J.-U. LEE, M.-Y. NAH, D.-G. KANG, K.-Y. AHN, H.-S. LEE, and K.-C. CHOI Cisplatin Decreases the Abundance of Aquaporin Water Channels in Rat Kidney J. Am. Soc. Nephrol., May 1, 2001; 12(5): 875 - 882. [Abstract] [Full Text]
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Y. Huang, R. Tracy, G. E. Walsberg, A. Makkinje, P. Fang, D. Brown, and A. N. Van Hoek Absence of aquaporin-4 water channels from kidneys of the desert rodent Dipodomys merriami merriami Am J Physiol Renal Physiol, May 1, 2001; 280(5): F794 - F802. [Abstract] [Full Text] [PDF]
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P. Downey, A. Sapirstein, E. O'Leary, T.-X. Sun, D. Brown, and J. V. Bonventre Renal concentrating defect in mice lacking group IV cytosolic phospholipase A2 Am J Physiol Renal Physiol, April 1, 2001; 280(4): F607 - F618. [Abstract] [Full Text] [PDF]
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T. Ma, S. Jayaraman, K. S. Wang, Y. Song, B. Yang, J. Li, J. A. Bastidas, and A. S. Verkman Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels Am J Physiol Cell Physiol, January 1, 2001; 280(1): C126 - C134. [Abstract] [Full Text] [PDF]
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 J.E. Melvin, H.-V. Nguyen, R.L. Evans, and G.E. Shull What Can Transgenic and Gene-targeted Mouse Models Teach Us about Salivary Gland Physiology? Advances in Dental Research, December 1, 2000; 14(1): 5 - 11. [Abstract] [PDF]
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Y. Song, B. Yang, M. A. Matthay, T. Ma, and A. S. Verkman Role of aquaporin water channels in pleural fluid dynamics Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1744 - C1750. [Abstract] [Full Text] [PDF]
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D. Promeneur, T.-H. Kwon, M. Yasui, G.-H. Kim, J. Frokiar, M. A. Knepper, P. Agre, and S. Nielsen Regulation of AQP6 mRNA and protein expression in rats in response to altered acid-base or water balance Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1014 - F1026. [Abstract] [Full Text] [PDF]
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T.-H. Kwon, U. H. Laursen, D. Marples, A. B. Maunsbach, M. A. Knepper, J. Frokiar, and S. Nielsen Altered expression of renal AQPs and Na+ transporters in rats with Lithium-induced NDI Am J Physiol Renal Physiol, September 1, 2000; 279(3): F552 - F564. [Abstract] [Full Text] [PDF]
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S. Rao and A. S. Verkman Analysis of organ physiology in transgenic mice Am J Physiol Cell Physiol, July 1, 2000; 279(1): C1 - C18. [Abstract] [Full Text] [PDF]
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Y. Song, N. Fukuda, C. Bai, T. Ma, M. A Matthay, and A S Verkman 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 J. Physiol., June 15, 2000; 525(3): 771 - 779. [Abstract] [Full Text] [PDF]
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E. ALBERTAZZI, D. ZANCHETTA, P. BARBIER, S. FARANDA, A. FRATTINI, P. VEZZONI, M. PROCACCIO, A. BETTINELLI, F. GUZZI, M. PARENTI, et al. Nephrogenic Diabetes Insipidus: Functional Analysis of New AVPR2Mutations Identified in Italian Families J. Am. Soc. Nephrol., June 1, 2000; 11(6): 1033 - 1043. [Abstract] [Full Text]
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V. Vallon, A. S. Verkman, and J. Schnermann Luminal hypotonicity in proximal tubules of aquaporin-1-knockout mice Am J Physiol Renal Physiol, June 1, 2000; 278(6): F1030 - F1033. [Abstract] [Full Text] [PDF]
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 A. S. Verkman, M. A. Matthay, and Y. Song Aquaporin water channels and lung physiology Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L867 - L879. [Abstract] [Full Text] [PDF]
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P. AGRE Aquaporin Water Channels in Kidney J. Am. Soc. Nephrol., April 1, 2000; 11(4): 764 - 777. [Full Text] [PDF]
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A.-M. Teichert, T. L. Miller, S. C. Tai, Y. Wang, X. Bei, G. B. Robb, M. J. Phillips, and P. A. Marsden In vivo expression profile of an endothelial nitric oxide synthase promoter-reporter transgene Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1352 - H1361. [Abstract] [Full Text] [PDF]
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J. D. Hoffert, V. Leitch, P. Agre, and L. S. King Hypertonic Induction of Aquaporin-5 Expression through an ERK-dependent Pathway J. Biol. Chem., March 17, 2000; 275(12): 9070 - 9077. [Abstract] [Full Text] [PDF]
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C. Masseguin, M. Corcoran, C. Carcenac, N. G. Daunton, A. Guell, A. S. Verkman, and J. Gabrion Altered gravity downregulates aquaporin-1 protein expression in choroid plexus J Appl Physiol, March 1, 2000; 88(3): 843 - 850. [Abstract] [Full Text] [PDF]
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A. N. van Hoek, T. Ma, B. Yang, A. S. Verkman, and D. Brown Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney Am J Physiol Renal Physiol, February 1, 2000; 278(2): F310 - F316. [Abstract] [Full Text] [PDF]
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B. Yang, N. Fukuda, A. van Hoek, M. A. Matthay, T. Ma, and A. S. Verkman Carbon Dioxide Permeability of Aquaporin-1 Measured in Erythrocytes and Lung of Aquaporin-1 Null Mice and in Reconstituted Proteoliposomes J. Biol. Chem., January 28, 2000; 275(4): 2686 - 2692. [Abstract] [Full Text] [PDF]
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 L. S. King, S. Nielsen, and P. Agre Respiratory Aquaporins in Lung Inflammation . The Night Is Young Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 8 - 10. [Full Text]
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J. SCHNERMANN Micropuncture Analysis of Tubuloglomerular Feedback Regulation in Transgenic Mice J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2614 - 2619. [Abstract] [Full Text]
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T. Matsuzaki, T. Suzuki, H. Koyama, S. Tanaka, and K. Takata Water Channel Protein AQP3 Is Present in Epithelia Exposed to the Environment of Possible Water Loss J. Histochem. Cytochem., October 1, 1999; 47(10): 1275 - 1286. [Abstract] [Full Text]
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T.-H. Kwon, J. Frokiaer, P. Fernandez-Llama, M. A. Knepper, and S. Nielsen Reduced abundance of aquaporins in rats with bilateral ischemia-induced acute renal failure: prevention by alpha -MSH Am J Physiol Renal Physiol, September 1, 1999; 277(3): F413 - F427. [Abstract] [Full Text] [PDF]
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