Human Molecular Genetics, 2000, Vol. 9, No. 20 2937-2945
© 2000 Oxford University Press
Mice lacking renal chloride channel, CLC-5, are a model for Dent’s disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis
Johns Hopkins University School of Medicine, Departments of Physiology and Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA, 1Division of Nephrology and Cell Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain Medical School, B-1200 Brussels, Belgium and 2Molecular Endocrinology Group, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
Nephrolithiasis (kidney stones) affects 5–10% of adults and is most commonly associated with hypercalciuria, which may be due to monogenic renal tubular disorders. One such hypercalciuric disorder is Dent’s disease, which is characterized by renal proximal tubular defects that include low molecular weight proteinuria, aminoaciduria and glycosuria, together with rickets in some patients. Dent’s disease is due to inactivating mutations of the renal-specific voltage-gated chloride channel, CLC-5, which is expressed in the proximal tubule, thick ascending limb and collecting duct. The subcellular localization of CLC-5 to the proximal tubular endosomes has suggested a role in endocytosis, and to facilitate in vivo investigations of CLC-5 in Dent’s disease we generated mice lacking CLC-5 by targeted gene disruption. CLC-5-deficient mice developed renal tubular defects which included low molecular weight (<70 kDa) proteinuria, generalized aminoaciduria that was more pronounced for neutral and polar amino acids, and glycosuria. They also developed hypercalciuria and renal calcium deposits and some had deformities of the spine. Furthermore, endocytosis as assessed by horseradish peroxidase uptake in the proximal tubule was severely impaired in CLC-5-deficient mice, thereby demonstrating a role for CLC-5 in endosomal uptake of low molecular weight proteins. Thus, CLC-5-deficient mice provide a model for Dent’s disease and this will help in elucidating the function of this chloride channel in endocytosis and renal calcium homeostasis.
+ These authors contributed equally to this work
§ To whom correspondence should be addressed. Tel: +1 410 955 7166; Fax: +1 410 955 0461; Email: wguggino@bs.jhmi.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Nevo, M. Chol, A. Bailleux, V. Kalatzis, L. Morisset, O. Devuyst, M.-C. Gubler, and C. Antignac Renal phenotype of the cystinosis mouse model is dependent upon genetic background Nephrol. Dial. Transplant., October 21, 2009; (2009) gfp553v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Guggino Can we generate new hypotheses about Dent's disease from gene analysis of a mouse model? Exp Physiol, February 1, 2009; 94(2): 191 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maritzen, D. J. Keating, I. Neagoe, A. A. Zdebik, and T. J. Jentsch Role of the Vesicular Chloride Transporter ClC-3 in Neuroendocrine Tissue J. Neurosci., October 15, 2008; 28(42): 10587 - 10598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wright, M. M. Morales, J. Sousa-Menzes, D. Ornellas, J. Sipes, Y. Cui, I. Cui, P. Hulamm, V. Cebotaru, L. Cebotaru, et al. Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney Physiol Genomics, May 1, 2008; 33(3): 341 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-Y. Chen and T.-C. Hwang CLC-0 and CFTR: Chloride Channels Evolved From Transporters Physiol Rev, April 1, 2008; 88(2): 351 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Terryn, F. Jouret, F. Vandenabeele, I. Smolders, M. Moreels, O. Devuyst, P. Steels, and E. V. Kerkhove A primary culture of mouse proximal tubular cells, established on collagen-coated membranes Am J Physiol Renal Physiol, August 1, 2007; 293(2): F476 - F485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nielsen, P. J. Courtoy, C. Jacobsen, G. Dom, W. R. Lima, M. Jadot, T. E. Willnow, O. Devuyst, and E. I. Christensen Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells PNAS, March 27, 2007; 104(13): 5407 - 5412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jouret, A. Bernard, C. Hermans, G. Dom, S. Terryn, T. Leal, P. Lebecque, J.-J. Cassiman, B. J. Scholte, H. R. de Jonge, et al. Cystic Fibrosis Is Associated with a Defect in Apical Receptor-Mediated Endocytosis in Mouse and Human Kidney J. Am. Soc. Nephrol., March 1, 2007; 18(3): 707 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Jentsch Chloride and the endosomal-lysosomal pathway: emerging roles of CLC chloride transporters J. Physiol., February 1, 2007; 578(3): 633 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ludwig, B. Utsch, and L. A. H. Monnens Recent advances in understanding the clinical and genetic heterogeneity of Dent's disease Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2708 - 2717. [Full Text] [PDF]
|
|
|
|
|
|
M. Poet, U. Kornak, M. Schweizer, A. A. Zdebik, O. Scheel, S. Hoelter, W. Wurst, A. Schmitt, J. C. Fuhrmann, R. Planells-Cases, et al. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6 PNAS, September 12, 2006; 103(37): 13854 - 13859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tosetto, G. M. Ghiggeri, F. Emma, G. Barbano, A. Carrea, G. Vezzoli, R. Torregrossa, M. Cara, G. Ripanti, A. Ammenti, et al. Phenotypic and genetic heterogeneity in Dent's disease--the results of an Italian collaborative study Nephrol. Dial. Transplant., September 1, 2006; 21(9): 2452 - 2463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sirac, F. Bridoux, C. Carrion, O. Devuyst, B. Fernandez, J.-M. Goujon, C. E. Hamel, J.-C. Aldigier, G. Touchard, and M. Cogne Role of the monoclonal {kappa} chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi syndrome Blood, July 15, 2006; 108(2): 536 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Hryciw, J. Ekberg, C. Ferguson, A. Lee, D. Wang, R. G. Parton, C. A. Pollock, C. C. Yun, and P. Poronnik Regulation of Albumin Endocytosis by PSD95/Dlg/ZO-1 (PDZ) Scaffolds: INTERACTION OF Na+-H+ EXCHANGE REGULATORY FACTOR-2 WITH ClC-5 J. Biol. Chem., June 9, 2006; 281(23): 16068 - 16077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-F. van den Hove, K. Croizet-Berger, F. Jouret, S. E. Guggino, W. B. Guggino, O. Devuyst, and P. J. Courtoy The Loss of the Chloride Channel, ClC-5, Delays Apical Iodide Efflux and Induces a Euthyroid Goiter in the Mouse Thyroid Gland Endocrinology, March 1, 2006; 147(3): 1287 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Picard, M. Van Abel, C. Campone, M. Seiler, M. Bloch-Faure, J. G.J. Hoenderop, J. Loffing, P. Meneton, R. J.M. Bindels, M. Paillard, et al. Tissue Kallikrein-Deficient Mice Display a Defect in Renal Tubular Calcium Absorption J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3602 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Caruso-Neves, S.-H. Kwon, and W. B. Guggino Albumin endocytosis in proximal tubule cells is modulated by angiotensin II through an AT2 receptor-mediated protein kinase B activation PNAS, November 29, 2005; 102(48): 17513 - 17518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, H. Cai, L. Cebotaru, D. H. Hryciw, E. J. Weinman, M. Donowitz, S. E. Guggino, and W. B. Guggino ClC-5: role in endocytosis in the proximal tubule Am J Physiol Renal Physiol, October 1, 2005; 289(4): F850 - F862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Jentsch Chloride Transport in the Kidney: Lessons from Human Disease and Knockout Mice J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1549 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. W. Moe and O. Bonny Genetic Hypercalciuria J. Am. Soc. Nephrol., March 1, 2005; 16(3): 729 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Hryciw, J. Ekberg, A. Lee, I. L. Lensink, S. Kumar, W. B. Guggino, D. I. Cook, C. A. Pollock, and P. Poronnik Nedd4-2 Functionally Interacts with ClC-5: INVOLVEMENT IN CONSTITUTIVE ALBUMIN ENDOCYTOSIS IN PROXIMAL TUBULE CELLS J. Biol. Chem., December 31, 2004; 279(53): 54996 - 55007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Babini and M. Pusch A Two-Holed Story: Structural Secrets About ClC Proteins Become Unraveled? Physiology, October 1, 2004; 19(5): 293 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Wagner, K. E. Finberg, S. Breton, V. Marshansky, D. Brown, and J. P. Geibel Renal Vacuolar H+-ATPase Physiol Rev, October 1, 2004; 84(4): 1263 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-C. Pham, O. Devuyst, P.-T. Pham, N. Matsumoto, R. N. G. Shih, O. D. Jo, N. Yanagawa, and A. M. Sun Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb cells Am J Physiol Renal Physiol, October 1, 2004; 287(4): F747 - F752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Cutillas, R. J. Chalkley, K. C. Hansen, R. Cramer, A. G. W. Norden, M. D. Waterfield, A. L. Burlingame, and R. J. Unwin The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells Am J Physiol Renal Physiol, September 1, 2004; 287(3): F353 - F364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Hryciw, Y. Wang, O. Devuyst, C. A. Pollock, P. Poronnik, and W. B. Guggino Cofilin Interacts with ClC-5 and Regulates Albumin Uptake in Proximal Tubule Cell Lines J. Biol. Chem., October 10, 2003; 278(41): 40169 - 40176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mohammad-Panah, R. Harrison, S. Dhani, C. Ackerley, L.-J. Huan, Y. Wang, and C. E. Bear The Chloride Channel ClC-4 Contributes to Endosomal Acidification and Trafficking J. Biol. Chem., August 1, 2003; 278(31): 29267 - 29277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Christensen, O. Devuyst, G. Dom, R. Nielsen, P. Van Der Smissen, P. Verroust, M. Leruth, W. B. Guggino, and P. J. Courtoy Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules PNAS, July 8, 2003; 100(14): 8472 - 8477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Carballo-Trujillo, V. Garcia-Nieto, F. J. Moya-Angeler, M. Anton-Gamero, C. Loris, S. Mendez-Alvarez, and F. Claverie-Martin Novel truncating mutations in the ClC-5 chloride channel gene in patients with Dent's disease Nephrol. Dial. Transplant., April 1, 2003; 18(4): 717 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Strange From Genes to Integrative Physiology: Ion Channel and Transporter Biology in Caenorhabditis elegans Physiol Rev, April 1, 2003; 83(2): 377 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Frick and D. A. Bushinsky Molecular Mechanisms of Primary Hypercalciuria J. Am. Soc. Nephrol., April 1, 2003; 14(4): 1082 - 1095. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cao, G. Yang, T. L. Timme, T. Saika, L. D. Truong, T. Satoh, A. Goltsov, S. H. Park, T. Men, N. Kusaka, et al. Disruption of the Caveolin-1 Gene Impairs Renal Calcium Reabsorption and Leads to Hypercalciuria and Urolithiasis Am. J. Pathol., April 1, 2003; 162(4): 1241 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Isnard-Bagnis, N. Da Silva, V. Beaulieu, A. S. L. Yu, D. Brown, and S. Breton Detection of ClC-3 and ClC-5 in epididymal epithelium: immunofluorescence and RT-PCR after LCM Am J Physiol Cell Physiol, January 1, 2003; 284(1): C220 - C232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Devuyst and W. B. Guggino Chloride channels in the kidney: lessons learned from knockout animals Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1176 - F1191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Thevenod Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins Am J Physiol Cell Physiol, September 1, 2002; 283(3): C651 - C672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. X. Weng, B. F. Godley, G. F. Jin, N. J. Mangini, B. G. Kennedy, A. S. L. Yu, and N. K. Wills Oxidant and antioxidant modulation of chloride channels expressed in human retinal pigment epithelium Am J Physiol Cell Physiol, September 1, 2002; 283(3): C839 - C849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Jentsch, V. Stein, F. Weinreich, and A. A. Zdebik Molecular Structure and Physiological Function of Chloride Channels Physiol Rev, April 1, 2002; 82(2): 503 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, T. Tsunenari, K.-W. Yau, and J. Nathans The vitelliform macular dystrophy protein defines a new family of chloride channels PNAS, March 19, 2002; 99(6): 4008 - 4013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Birn, T. E. Willnow, R. Nielsen, A. G. W. Norden, C. Bonsch, S. K. Moestrup, E. Nexo, and E. I. Christensen Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B12 Am J Physiol Renal Physiol, March 1, 2002; 282(3): F408 - F416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mohammad-Panah, C. Ackerley, J. Rommens, M. Choudhury, Y. Wang, and C. E. Bear The Chloride Channel ClC-4 Co-localizes with Cystic Fibrosis Transmembrane Conductance Regulator and May Mediate Chloride Flux across the Apical Membrane of Intestinal Epithelia J. Biol. Chem., January 4, 2002; 277(1): 566 - 574. [Abstract] [Full Text]
|
|
|
|
|
|
A. Vandewalle Diversity within the CLC chloride channel family involved in inherited diseases: from plasma membranes to acidic organelles Nephrol. Dial. Transplant., January 1, 2002; 17(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
J A Sayer, G S Stewart, S H Boese, M A Gray, S H S Pearce, T H J Goodship, and N L Simmons The voltage-dependent Cl- channel ClC-5 and plasma membrane Cl- conductances of mouse renal collecting duct cells (mIMCD-3) J. Physiol., November 1, 2001; 536(3): 769 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fares and I. Greenwald Genetic Analysis of Endocytosis in Caenorhabditis elegans: Coelomocyte Uptake Defective Mutants Genetics, September 1, 2001; 159(1): 133 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Wills and P. Fong ClC Chloride Channels in Epithelia: Recent Progress and Remaining Puzzles Physiology, August 1, 2001; 16(4): 161 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Edmonds, I. V. Silva, W. B. Guggino, R. B. Butler, P. L. Zeitlin, and C. J. Blaisdell Pre- and Postnatal Lung Development, Maturation, and Plasticity: ClC-5: ontogeny of an alternative chloride channel in respiratory epithelia Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L501 - L507. [Abstract] [Full Text] [PDF]
|
|