Background/Aims: Tenc1 (also known as tensin2) is an integrin-associated focal adhesion molecule that is broadly expressed in mouse tissues including the liver, muscle, heart and kidney. A mouse strain carrying mutated Tenc1, the ICR-derived glomerulonephritis (ICGN) strain, develops severe nephrotic syndrome. Methods: To elucidate the function of Tenc1 in the kidney, Tenc1ICGN was introduced into 2 genetic backgrounds, i.e. DBA/2J (D2) and C57BL/6J (B6), strains that are respectively susceptible and resistant to chronic kidney disease. Results: Biochemical and histological analysis revealed that homozygous Tenc1ICGN mice develop nephrotic syndrome on the D2 background (D2GN) but not on the B6 background (B6GN). Initially, abnormal assembly and maturation of glomerular basement membrane (GBM) were observed, and subsequently effacement of podocyte foot processes was noted in the kidneys of D2GN but not B6GN mice. These defects are likely to be involved in the integrin signaling pathway. Conclusion: This study suggests that Tenc1 contributes to the maintenance of GBM structures and that the genetic background influences the severity of nephrotic syndrome.

Caridi G, Trivelli A, Sanna-Cherchi S, Perfumo F, Ghiggeri GM: Familial forms of nephrotic syndrome. Pediatr Nephrol 2010;25:241-252.
Machuca E, Benoit G, Antignac C: Genetics of nephrotic syndrome: connecting molecular genetics to podocyte physiology. Hum Mol Genet 2009;18:R185-R194.
Jalanko H: Congenital nephrotic syndrome. Pediatr Nephrol 2009;24:2121-2128.
Tryggvason K, Patrakka J, Wartiovaara J: Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med 2006;354:1387-1401.
Miner JH: Renal basement membrane components. Kidney Int 1999;56:2016-2024.
Harvey SJ, Zheng K, Sado Y, Naito I, Ninomiya Y, Jacobs RM, Hudson BG, Thorner PS: Role of distinct type IV collagen networks in glomerular development and function. Kidney Int 1998;54:1857-1866.
Miner JH, Go G, Cunningham J, Patton BL, Jarad G: Transgenic isolation of skeletal muscle and kidney defects in laminin β2 mutant mice: implications for Pierson syndrome. Development 2006;133:967-975.
Noakes PG, Miner JH, Gautam M, Cunningham JM, Sanes JR, Merlie JP: The renal glomerulus of mice lacking s-laminin/laminin β2: nephrosis despite molecular compensation by laminin β1. Nat Genet 1995;10:400-406.
Cosgrove D, Meehan DT, Grunkemeyer JA, Kornak JM, Sayers R, Hunter WJ, Samuelson GC: Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome. Genes Dev 1996;10:2981-2992.
Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K: Positionally cloned gene for a novel glomerular protein - nephrin - is mutated in congenital nephrotic syndrome. Mol Cell 1998;1:575-582.
Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C: NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000;24:349-354.
Kreidberg JA, Donovan MJ, Goldstein SL, Rennke H, Shepherd K, Jones RC, Jaenisch R: α3β1 integrin has a crucial role in kidney and lung organogenesis. Development 1996;122:3537-3547.
Dai C, Stolz DB, Bastacky SI, St-Arnaud R, Wu C, Dedhar S, Liu Y: Essential role of integrin-linked kinase in podocyte biology: bridging the integrin and slit diaphragm signaling. J Am Soc Nephrol 2006;17:2164-2175.
Ma H, Togawa A, Soda K, Zhang J, Lee S, Ma M, Yu Z, Ardito T, Czyzyk J, Diggs L, Joly D, Hatakeyama S, Kawahara E, Holzman L, Guan JL, Ishibe S: Inhibition of podocyte FAK protects against proteinuria and foot process effacement. J Am Soc Nephrol 2010;21:1145-1156.
El-Aouni C, Herbach N, Blattner SM, Henger A, Rastaldi MP, Jarad G, Miner JH, Moeller MJ, St-Arnaud R, Dedhar S, Holzman LB, Wanke R, Kretzler M: Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis. J Am Soc Nephrol 2006;17:1334-1344.
Kanasaki K, Kanda Y, Palmsten K, Tanjore H, Lee SB, Lebleu VS, Gattone VH Jr, Kalluri R: Integrin β1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus. Dev Biol 2008;313:584-593.
Ogura A, Asano T, Matsuda J, Takano K, Nakagawa M, Fukui M: Characteristics of mutant mice (ICGN) with spontaneous renal lesion: a new model for human nephrotic syndrome. Lab Anim 1989;23:169-174.
Cho A-R, Uchio-Yamada K, Torigai T, Miyamoto T, Miyoshi I, Matsuda J, Kurosawa T, Kon Y, Asano A, Sasaki N, Agui T: Deficiency of the tensin2 gene in the ICGN mouse, an animal model for congenital nephrotic syndrome. Mamm Genome 2006;17:407-416.
Chen H, Duncan IC, Bozorgchami H, Lo SH: Tensin1 and a previously undocumented family member, tensin2, positively regulate cell migration. Proc Natl Acad Sci USA 2002;99:733-738.
Lo SH: Tensin. Int J Biochem Cell Biol 2004;36:31-34.
Hafizi S, Gustafsson A, Oslakovic C, Idevall-Hagren O, Tengholm A, Sperandio O, Villoutreix BO, Dahlbäck B: Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane. Biochem Biophys Res Commun 2010;399:396-401.
Hafizi S, Sernstad E, Swinny JD, Gomez MF, Dahlbäck B: Individual domains of Tensin2 exhibit distinct subcellular localisations and migratory effects. Int J Biochem Cell Biol 2010;42:52-61.
Nishino T, Sasaki N, Nagasaki K, Ahmad Z, Agui T: Genetic background strongly influences the severity of glomerulosclerosis in mice. J Vet Med Sci 2010;72:1313-1318.
Kato T, Mizuno-Horikawa Y, Mizuno S: Decreases in podocin, CD2-associated protein (CD2AP) and tensin2 may be involved in albuminuria during septic acute renal failure. J Vet Med Sci 2011;73:1579-1584.
Takemoto M, Asker N, Gerhardt H, Lundkvist A, Johansson BR, Saito Y, Betsholtz C: A new method for large scale isolation of kidney glomeruli from mice. Am J Pathol 2002;161:799-805.
Sheehan S, Tsaih SW, King BL, Stanton C, Churchill GA, Paigen B, DiPetrillo K: Genetic analysis of albuminuria in a cross between C57BL/6J and DBA/2J mice. Am J Physiol Renal Physiol 2007;293:F1649-F1656.
Baleato RM, Guthrie PL, Gubler MC, Ashman LK, Roselli S: Deletion of CD151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane. Am J Pathol 2008;173:927-937.
Andrews KL, Mudd JL, Li C, Miner JH: Quantitative trait loci influence renal disease progression in a mouse model of Alport syndrome. Am J Pathol 2002;160:721-730.
Kang JS, Wang XP, Miner JH, Morello R, Sado Y, Abrahamson DR, Borza DB: Loss of α3/α4 (IV) collagen from the glomerular basement membrane induces a strain-dependent isoform switch to α5α6 (IV) collagen associated with longer renal survival in Col4a3-/- Alport mice. J Am Soc Nephrol 2006;17:1962-1969.
Roselli S, Heidet L, Sich M, Henger A, Kretzler M, Gubler MC, Antignac C: Early glomerular filtration defect and severe renal disease in podocin-deficient mice. Mol Cell Biol 2004;24:550-560.
Jarad G, Cunningham J, Shaw AS, Miner JH: Proteinuria precedes podocyte abnormalities in Lamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest 2006;116:2272-2279.
Chan LK, Ko FC, Ng IO, Yam JW: Deleted in liver cancer 1 (DLC1) utilizes a novel binding site for tensin2 PTB domain interaction and is required for tumor-suppressive function. PLoS One 2009;4:e5572.
Zhu J, Sun N, Aoudjit L, Li H, Kawachi H, Lemay S, Takano T: Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes. Kidney Int 2008;73:556-566.
Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A, Egger L, Lecha RL, Borner C, Pavenstädt H, Shaw AS, Walz G, Benzing T: Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol 2003;23:4917-4928.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.