This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Roselli, S.
Right arrow Articles by Antignac, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roselli, S.
Right arrow Articles by Antignac, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2004, p. 550-560, Vol. 24, No. 2
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.2.550-560.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Early Glomerular Filtration Defect and Severe Renal Disease in Podocin-Deficient Mice

Séverine Roselli,1 Laurence Heidet,1 Mireille Sich,1 Anna Henger,2 Matthias Kretzler,2 Marie-Claire Gubler,1 and Corinne Antignac1,3*

INSERM U574, Hôpital Necker-Enfants Malades, Université René Descartes,1 Service de Génétique, Hôpital Necker-Enfants Malades, Paris, France,3 Nephrology Center, University of Munich, Munich, Germany2

Received 7 August 2003/ Returned for modification 23 September 2003/ Accepted 8 October 2003

Podocytes are specialized epithelial cells covering the basement membrane of the glomerulus in the kidney. The molecular mechanisms underlying the role of podocytes in glomerular filtration are still largely unknown. We generated podocin-deficient (Nphs2-/-) mice to investigate the function of podocin, a protein expressed at the insertion of the slit diaphragm in podocytes and defective in a subset of patients with steroid-resistant nephrotic syndrome and focal and segmental glomerulosclerosis. Nphs2-/- mice developed proteinuria during the antenatal period and died a few days after birth from renal failure caused by massive mesangial sclerosis. Electron microscopy revealed the extensive fusion of podocyte foot processes and the lack of a slit diaphragm in the remaining foot process junctions. Using real-time PCR and immunolabeling, we showed that the expression of other slit diaphragm components was modified in Nphs2-/- kidneys: the expression of the nephrin gene was downregulated, whereas that of the ZO1 and CD2AP genes appeared to be upregulated. Interestingly, the progression of the renal disease, as well as the presence or absence of renal vascular lesions, depends on the genetic background. Our data demonstrate the crucial role of podocin in the establishment of the glomerular filtration barrier and provide a suitable model for mapping and identifying modifier genes involved in glomerular diseases caused by podocyte injuries.

* Corresponding author. Mailing address: INSERM U574, Tour Lavoisier, 6ème Étage, Hôpital Necker-Enfants Malades, 75743 Paris, Cedex 15, France. Phone: 33-1-44-49-50-98. Fax: 33-1-44-49-02-90. E-mail: antignac{at}necker.fr.

Molecular and Cellular Biology, January 2004, p. 550-560, Vol. 24, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.2.550-560.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Arnould, C., Lelievre-Pegorier, M., Ronco, P., Lelongt, B. (2009). MMP9 Limits Apoptosis and Stimulates Branching Morphogenesis During Kidney Development. J. Am. Soc. Nephrol. 20: 2171-2180 [Abstract] [Full Text]  
  • Mollet, G., Ratelade, J., Boyer, O., Muda, A. O., Morisset, L., Lavin, T. A., Kitzis, D., Dallman, M. J., Bugeon, L., Hubner, N., Gubler, M.-C., Antignac, C., Esquivel, E. L. (2009). Podocin Inactivation in Mature Kidneys Causes Focal Segmental Glomerulosclerosis and Nephrotic Syndrome. J. Am. Soc. Nephrol. 20: 2181-2189 [Abstract] [Full Text]  
  • Pollak, M. R. (2009). Surprising Results following Conditional Podocyte Inactivation. J. Am. Soc. Nephrol. 20: 2086-2088 [Full Text]  
  • Giardino, L., Armelloni, S., Corbelli, A., Mattinzoli, D., Zennaro, C., Guerrot, D., Tourrel, F., Ikehata, M., Li, M., Berra, S., Carraro, M., Messa, P., Rastaldi, M. P. (2009). Podocyte Glutamatergic Signaling Contributes to the Function of the Glomerular Filtration Barrier. J. Am. Soc. Nephrol. 20: 1929-1940 [Abstract] [Full Text]  
  • Harita, Y., Kurihara, H., Kosako, H., Tezuka, T., Sekine, T., Igarashi, T., Ohsawa, I., Ohta, S., Hattori, S. (2009). Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1. J. Biol. Chem. 284: 8951-8962 [Abstract] [Full Text]  
  • Baleato, R. M., Guthrie, P. L., Gubler, M.-C., Ashman, L. K., Roselli, S. (2008). Deletion of Cd151 Results in a Strain-Dependent Glomerular Disease Due to Severe Alterations of the Glomerular Basement Membrane. Am. J. Pathol. 173: 927-937 [Abstract] [Full Text]  
  • Ratelade, J., Lavin, T. A., Muda, A. O., Morisset, L., Mollet, G., Boyer, O., Chen, D. S., Henger, A., Kretzler, M., Hubner, N., Thery, C., Gubler, M.-C., Montagutelli, X., Antignac, C., Esquivel, E. L. (2008). Maternal Environment Interacts with Modifier Genes to Influence Progression of Nephrotic Syndrome. J. Am. Soc. Nephrol. 19: 1491-1499 [Abstract] [Full Text]  
  • Harita, Y., Kurihara, H., Kosako, H., Tezuka, T., Sekine, T., Igarashi, T., Hattori, S. (2008). Neph1, a Component of the Kidney Slit Diaphragm, Is Tyrosine-phosphorylated by the Src Family Tyrosine Kinase and Modulates Intracellular Signaling by Binding to Grb2. J. Biol. Chem. 283: 9177-9186 [Abstract] [Full Text]  
  • Nakhoul, F., Khankin, E., Yaccob, A., Kawachi, H., Karram, T., Awaad, H., Nakhoul, N., Hoffman, A., Abassi, Z. (2008). Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic syndrome. Am. J. Physiol. Renal Physiol. 294: F628-F637 [Abstract] [Full Text]  
  • Quaggin, S. E., Kreidberg, J. A. (2008). Development of the renal glomerulus: good neighbors and good fences. Development 135: 609-620 [Abstract] [Full Text]  
  • Li, Y., Kang, Y. S., Dai, C., Kiss, L. P., Wen, X., Liu, Y. (2008). Epithelial-to-Mesenchymal Transition Is a Potential Pathway Leading to Podocyte Dysfunction and Proteinuria. Am. J. Pathol. 172: 299-308 [Abstract] [Full Text]  
  • Brukamp, K., Jim, B., Moeller, M. J., Haase, V. H. (2007). Hypoxia and podocyte-specific Vhlh deletion confer risk of glomerular disease. Am. J. Physiol. Renal Physiol. 293: F1397-F1407 [Abstract] [Full Text]  
  • Holthofer, H. (2007). Molecular architecture of the glomerular slit diaphragm: lessons learnt for a better understanding of disease pathogenesis. Nephrol Dial Transplant 22: 2124-2128 [Full Text]  
  • Jefferson, J. A., Shankland, S. J. (2007). Familial nephrotic syndrome: PLCE1 enters the fray. Nephrol Dial Transplant 22: 1849-1852 [Full Text]  
  • Caridi, G., Dagnino, M., Carrea, A., Massella, L., Amore, A., Emma, F., Coppo, R., Perfumo, F., Ghiggeri, G. M. (2007). Lack of cardiac anomalies in children with NPHS2 mutations. Nephrol Dial Transplant 22: 1477-1479 [Full Text]  
  • Peltier, J., Bellocq, A., Perez, J., Doublier, S., Dubois, Y.-C. X., Haymann, J.-P., Camussi, G., Baud, L. (2006). Calpain Activation and Secretion Promote Glomerular Injury in Experimental Glomerulonephritis: Evidence from Calpastatin-Transgenic Mice. J. Am. Soc. Nephrol. 17: 3415-3423 [Abstract] [Full Text]  
  • Quack, I., Rump, L. C., Gerke, P., Walther, I., Vinke, T., Vonend, O., Grunwald, T., Sellin, L. (2006). beta-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity. Proc. Natl. Acad. Sci. USA 103: 14110-14115 [Abstract] [Full Text]  
  • Dai, C., Stolz, D. B., Bastacky, S. I., St.-Arnaud, R., Wu, C., Dedhar, S., Liu, Y. (2006). Essential Role of Integrin-Linked Kinase in Podocyte Biology: Bridging the Integrin and Slit Diaphragm Signaling. J. Am. Soc. Nephrol. 17: 2164-2175 [Abstract] [Full Text]  
  • Tryggvason, K., Patrakka, J., Wartiovaara, J. (2006). Hereditary proteinuria syndromes and mechanisms of proteinuria.. NEJM 354: 1387-1401 [Full Text]  
  • Juhila, J., Roozendaal, R., Lassila, M., Verbeek, S. J., Holthofer, H. (2006). Podocyte Cell-Specific Expression of Doxycycline Inducible Cre Recombinase in Mice. J. Am. Soc. Nephrol. 17: 648-654 [Abstract] [Full Text]  
  • Winn, M. P., Daskalakis, N., Spurney, R. F., Middleton, J. P. (2006). Unexpected Role of TRPC6 Channel in Familial Nephrotic Syndrome: Does It Have Clinical Implications?. J. Am. Soc. Nephrol. 17: 378-387 [Full Text]  
  • Frishberg, Y., Feinstein, S., Rinat, C., Becker-Cohen, R., Lerer, I., Raas-Rothschild, A., Ferber, B., Nir, A. (2006). The Heart of Children with Steroid-Resistant Nephrotic Syndrome: Is It All Podocin?. J. Am. Soc. Nephrol. 17: 227-231 [Abstract] [Full Text]  
  • Wang, L., Fields, T. A., Pazmino, K., Dai, Q., Burchette, J. L., Howell, D. N., Coffman, T. M., Spurney, R. F. (2005). Activation of G{alpha}q-Coupled Signaling Pathways in Glomerular Podocytes Promotes Renal Injury. J. Am. Soc. Nephrol. 16: 3611-3622 [Abstract] [Full Text]  
  • Nakhoul, F., Ramadan, R., Khankin, E., Yaccob, A., Kositch, Z., Lewin, M., Assady, S., Abassi, Z. (2005). Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome: different effects of antiproteinuric therapies. Am. J. Physiol. Renal Physiol. 289: F880-F890 [Abstract] [Full Text]  
  • Matsusaka, T., Xin, J., Niwa, S., Kobayashi, K., Akatsuka, A., Hashizume, H., Wang, Q.-c., Pastan, I., Fogo, A. B., Ichikawa, I. (2005). Genetic Engineering of Glomerular Sclerosis in the Mouse via Control of Onset and Severity of Podocyte-Specific Injury. J. Am. Soc. Nephrol. 16: 1013-1023 [Abstract] [Full Text]  
  • Gao, F., Maiti, S., Sun, G., Ordonez, N. G., Udtha, M., Deng, J. M., Behringer, R. R., Huff, V. (2004). The Wt1+/R394W Mouse Displays Glomerulosclerosis and Early-Onset Renal Failure Characteristic of Human Denys-Drash Syndrome. Mol. Cell. Biol. 24: 9899-9910 [Abstract] [Full Text]  
  • Fan, Q., Ding, J., Zhang, J., Guan, N., Deng, J. (2004). Effect of the Knockdown of Podocin mRNA on Nephrin and {alpha}-Actinin in Mouse Podocyte. Exp. Biol. Med. 229: 964-970 [Abstract] [Full Text]  
  • Benzing, T. (2004). Signaling at the Slit Diaphragm. J. Am. Soc. Nephrol. 15: 1382-1391 [Full Text]  
  • Ghiggeri, G. M., Carraro, M., Vincenti, F. (2004). Recurrent focal glomerulosclerosis in the era of genetics of podocyte proteins: theory and therapy. Nephrol Dial Transplant 19: 1036-1040 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»