|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 4, 2775-2779, January 26, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Medicine, Physiology, and
Pediatrics, Cardiovascular Research Institute, University of
California, San Francisco, California 94143-0521
Hereditary non-X-linked nephrogenic diabetes
insipidus (NDI) is caused by mutations in the aquaporin-2 (AQP2)
water channel. In transfected cells, the human disease-causing mutant
AQP2-T126M is retained at the endoplasmic reticulum (ER) where it is
functional and targetable to the plasma membrane with chemical
chaperones. A mouse knock-in model of NDI was generated by targeted
gene replacement using a Cre-loxP strategy. Along with T126M, mutations
H122S, N124S, and A125T were introduced to preserve the consensus
sequence for N-linked glycosylation found in human AQP2.
Breeding of heterozygous mice yielded the expected Mendelian
distribution with 26 homozygous mutant offspring of 99 live births. The
mutant mice appeared normal at 2-3 days after birth but failed to
thrive and generally died by day 6 if not given supplemental fluid.
Urine/serum analysis showed a urinary concentrating defect with serum
hyperosmolality and low urine osmolality that was not increased by a V2
vasopressin agonist. Northern blot analysis showed up-regulated
AQP2-T126M transcripts of identical size to wild-type AQP2. Immunoblots
showed complex glycosylation of wild-type AQP2 but mainly
endoglycosidase H-sensitive core glycosylation of AQP2-T126M indicating
ER-retention. Biochemical analysis revealed that the AQP2-T126M protein
was resistant to detergent solubilization. Kidneys from mutant mice showed collecting duct dilatation, papillary atrophy, and unexpectedly, some plasma membrane AQP2 staining. The severe phenotype of the AQP2
mutant mice compared with that of mice lacking kidney water channels
AQP1, AQP3, and AQP4 indicates a critical role for AQP2 in neonatal
renal function in mice. Our results establish a mouse model of human
autosomal NDI and provide the first in vivo biochemical data on a disease-causing AQP2 mutant.
Neonatal Mortality in an Aquaporin-2 Knock-in Mouse Model of
Recessive Nephrogenic Diabetes Insipidus*
*
This work was supported by National Institutes of Health
Grants DK35124, HL58198, 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.
To whom correspondence should be addressed: 1246 Health Sciences
E. Tower, Cardiovascular Research Inst., University of California, San
Francisco, San Francisco, CA 94143-0521. Tel.: 415-476-8530; Fax:
415-665-3847; E-mail: verkman@itsa.ucsf.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Wu, S. Kitamura, D. M. Truong, T. Rieg, V. Vallon, H. Sakurai, K. T. Bush, D. R. Vera, R. S. Ross, and S. K. Nigam {beta}1-Integrin is required for kidney collecting duct morphogenesis and maintenance of renal function Am J Physiol Renal Physiol, July 1, 2009; 297(1): F210 - F217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Verkman Aquaporins: translating bench research to human disease J. Exp. Biol., June 1, 2009; 212(11): 1707 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Sparrow, S. C. Boyle, R. S. Sams, B. Mazuruk, L. Zhang, G. W. Moeckel, S. L. Dunwoodie, and M. P. de Caestecker Placental Insufficiency Associated with Loss of Cited1 Causes Renal Medullary Dysplasia J. Am. Soc. Nephrol., April 1, 2009; 20(4): 777 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Yang, D. Zhao, and A. S. Verkman Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation FASEB J, February 1, 2009; 23(2): 503 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Suga, H. Nagasaki, T.-a. Kondo, Y. Okajima, C. Suzuki, N. Ozaki, H. Arima, T. Yamamoto, N. Ozaki, M. Akai, et al. Novel Treatment for Lithium-Induced Nephrogenic Diabetes Insipidus Rat Model Using the Sendai-Virus Vector Carrying Aquaporin 2 Gene Endocrinology, November 1, 2008; 149(11): 5803 - 5810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Tchekneva, Z. Khuchua, L. S. Davis, V. Kadkina, S. R. Dunn, S. Bachman, K. Ishibashi, E. M. Rinchik, R. C. Harris, M. M. Dikov, et al. Single Amino Acid Substitution in Aquaporin 11 Causes Renal Failure J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1955 - 1964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lang, V. Vallon, M. Knipper, and P. Wangemann Functional significance of channels and transporters expressed in the inner ear and kidney Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1187 - C1208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Shi, X. R. Cao, J. Qu, K. A. Volk, P. Kirby, R. A. Williamson, J. B. Stokes, and B. Yang Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2 Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1334 - F1344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-F. Huang, R.-H. He, C.-C. Sun, Y. Zhang, Q.-X. Meng, and Y.-Y. Ma Function of aquaporins in female and male reproductive systems Hum. Reprod. Update, November 1, 2006; 12(6): 785 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sohara, T. Rai, S.-S. Yang, K. Uchida, K. Nitta, S. Horita, M. Ohno, A. Harada, S. Sasaki, and S. Uchida Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation PNAS, September 19, 2006; 103(38): 14217 - 14222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang, D. Zhao, L. Qian, and A. S. Verkman Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion Am J Physiol Renal Physiol, August 1, 2006; 291(2): F465 - F472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. R. Cao, P. P. Shi, R. D. Sigmund, R. F. Husted, C. D. Sigmund, R. A. Williamson, J. B. Stokes, and B. Yang Mice heterozygous for beta-ENaC deletion have defective potassium excretion Am J Physiol Renal Physiol, July 1, 2006; 291(1): F107 - F115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Gooch, R. L. Guler, J. L. Barnes, and J. J. Toro Loss of calcineurin A{alpha} results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus J. Cell Sci., June 15, 2006; 119(12): 2468 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. McDill, S.-Z. Li, P. A. Kovach, L. Ding, and F. Chen Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation PNAS, May 2, 2006; 103(18): 6952 - 6957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rojek, E.-M. Fuchtbauer, T.-H. Kwon, J. Frokiaer, and S. Nielsen Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice PNAS, April 11, 2006; 103(15): 6037 - 6042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaki, T. Schoneberg, T. Al Ajrawi, A. N. Al Said, K. Sangkuhl, and H. Rompler Nephrogenic diabetes insipidus, thiazide treatment and renal cell carcinoma Nephrol. Dial. Transplant., April 1, 2006; 21(4): 1082 - 1086. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fenton, A. Shodeinde, and M. A. Knepper UT-A urea transporter promoter, UT-A{alpha}, targets principal cells of the renal inner medullary collecting duct Am J Physiol Renal Physiol, January 1, 2006; 290(1): F188 - F195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Morishita, T. Matsuzaki, M. Hara-chikuma, A. Andoo, M. Shimono, A. Matsuki, K. Kobayashi, M. Ikeda, T. Yamamoto, A. Verkman, et al. Disruption of Aquaporin-11 Produces Polycystic Kidneys following Vacuolization of the Proximal Tubule Mol. Cell. Biol., September 1, 2005; 25(17): 7770 - 7779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Verkman More than just water channels: unexpected cellular roles of aquaporins J. Cell Sci., August 1, 2005; 118(15): 3225 - 3232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Morishita, M. Tsutsui, H. Shimokawa, K. Sabanai, H. Tasaki, O. Suda, S. Nakata, A. Tanimoto, K.-Y. Wang, Y. Ueta, et al. Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms PNAS, July 26, 2005; 102(30): 10616 - 10621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fenton, A. Flynn, A. Shodeinde, C. P. Smith, J. Schnermann, and M. A. Knepper Renal Phenotype of UT-A Urea Transporter Knockout Mice J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1583 - 1592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang, Y. Song, D. Zhao, and A. S. Verkman Phenotype analysis of aquaporin-8 null mice Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1161 - C1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Nejsum, M. Zelenina, A. Aperia, J. Frokiaer, and S. Nielsen Bidirectional regulation of AQP2 trafficking and recycling: involvement of AQP2-S256 phosphorylation Am J Physiol Renal Physiol, May 1, 2005; 288(5): F930 - F938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Jeck, K. P. Schlingmann, S. C. Reinalter, M. Komhoff, M. Peters, S. Waldegger, and H. W. Seyberth Salt handling in the distal nephron: lessons learned from inherited human disorders Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2005; 288(4): R782 - R795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. M. Lam, B. C. B. Ko, S. Tam, R. Morris, J. Y. Yang, S. K. Chung, and S. S. M. Chung Osmotic Response Element-binding Protein (OREBP) Is an Essential Regulator of the Urine Concentrating Mechanism J. Biol. Chem., November 12, 2004; 279(46): 48048 - 48054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Joo, U. S. Jeon, G.-H. Kim, J. Park, Y. K. Oh, Y. S. Kim, C. Ahn, S. Kim, S. Y. Kim, J. S. Lee, et al. Antidiuretic action of oxytocin is associated with increased urinary excretion of aquaporin-2 Nephrol. Dial. Transplant., October 1, 2004; 19(10): 2480 - 2486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Amlal, S. Sheriff, and M. Soleimani Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1019 - C1030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lopez-Rodriguez, C. L. Antos, J. M. Shelton, J. A. Richardson, F. Lin, T. I. Novobrantseva, R. T. Bronson, P. Igarashi, A. Rao, and E. N. Olson Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression PNAS, February 24, 2004; 101(8): 2392 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hirano, C. Zuber, J. Roth, and M. Ziak The Proteasome Is Involved in the Degradation of Different Aquaporin-2 Mutants Causing Nephrogenic Diabetes Insipidus Am. J. Pathol., July 1, 2003; 163(1): 111 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang and A. S. Verkman Analysis of Double Knockout Mice Lacking Aquaporin-1 and Urea Transporter UT-B. EVIDENCE FOR UT-B-FACILITATED WATER TRANSPORT IN ERYTHROCYTES J. Biol. Chem., September 20, 2002; 277(39): 36782 - 36786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Lin, D. G. Bichet, S. Sasaki, M. Kuwahara, M.-F. Arthus, M. Lonergan, and Y.-F. Lin Two Novel Aquaporin-2 Mutations Responsible for Congenital Nephrogenic Diabetes Insipidus in Chinese Families J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2694 - 2700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Takahashi, H. L. Brooks, J. B. Wade, W. Liu, Y. Kondo, S. Ito, M. A. Knepper, and O. Smithies Posttranscriptional Compensation for Heterozygous Disruption of the Kidney-Specific NaK2Cl Cotransporter Gene J. Am. Soc. Nephrol., March 1, 2002; 13(3): 604 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bankir Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects Cardiovasc Res, August 15, 2001; 51(3): 372 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Levin, P. M. Haggie, L. Vetrivel, and A. S. Verkman Diffusion in the Endoplasmic Reticulum of an Aquaporin-2 Mutant Causing Human Nephrogenic Diabetes Insipidus J. Biol. Chem., June 8, 2001; 276(24): 21331 - 21336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li and A. S. Verkman Impaired Hearing in Mice Lacking Aquaporin-4 Water Channels J. Biol. Chem., August 10, 2001; 276(33): 31233 - 31237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. SHIELS, S. BASSNETT, K. VARADARAJ, R. MATHIAS, K. AL-GHOUL, J. KUSZAK, D. DONOVIEL, S. LILLEBERG, G. FRIEDRICH, and B. ZAMBROWICZ Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice Physiol Genomics, December 21, 2001; 7(2): 179 - 186. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |