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 Ciani, L.
Right arrow Articles by ffrench-Constant, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ciani, L.
Right arrow Articles by ffrench-Constant, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2003, p. 3575-3582, Vol. 23, No. 10
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.10.3575-3582.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mice Lacking the Giant Protocadherin mFAT1 Exhibit Renal Slit Junction Abnormalities and a Partially Penetrant Cyclopia and Anophthalmia Phenotype

Lorenza Ciani,1 Anjla Patel,1 Nicholas D. Allen,2 and Charles ffrench-Constant1*

Departments of Medical Genetics and Pathology, University of Cambridge, Cambridge CB2 1QP,1 Neurobiology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom2

Received 16 July 2002/ Returned for modification 31 January 2003/ Accepted 21 February 2003

While roles in adhesion and morphogenesis have been documented for classical cadherins, the nonclassical cadherins are much less well understood. Here we have examined the functions of the giant protocadherin FAT by generating a transgenic mouse lacking mFAT1. These mice exhibit perinatal lethality, most probably caused by loss of the renal glomerular slit junctions and fusion of glomerular epithelial cell processes (podocytes). In addition, some mFAT1-/- mice show defects in forebrain development (holoprosencephaly) and failure of eye development (anophthalmia). In contrast to Drosophila, where FAT acts as a tumor suppressor gene, we found no evidence for abnormalities of proliferation in two tissues (skin and central nervous system [CNS]) containing stem and precursor cell populations and in which FAT is expressed strongly. Our results confirm a necessary role for FAT1 in the modified adhesion junctions of the renal glomerular epithelial cell and reveal hitherto unsuspected roles for FAT1 in CNS development.

* Corresponding author. Mailing address: Department of Medical Genetics and Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, United Kingdom. Phone: 44-1223-333723. Fax: 44-1223-333346. E-mail: cfc{at}mole.bio.cam.ac.uk.

Molecular and Cellular Biology, May 2003, p. 3575-3582, Vol. 23, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.10.3575-3582.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Hou, R., Sibinga, N. E. S. (2009). Atrophin Proteins Interact with the Fat1 Cadherin and Regulate Migration and Orientation in Vascular Smooth Muscle Cells. J. Biol. Chem. 284: 6955-6965 [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]  
  • Quaggin, S. E., Kreidberg, J. A. (2008). Development of the renal glomerulus: good neighbors and good fences. Development 135: 609-620 [Abstract] [Full Text]  
  • He, L., Sun, Y., Takemoto, M., Norlin, J., Tryggvason, K., Samuelsson, T., Betsholtz, C. (2008). The Glomerular Transcriptome and a Predicted Protein-Protein Interaction Network. J. Am. Soc. Nephrol. 19: 260-268 [Abstract] [Full Text]  
  • Braun, G. S., Kretzler, M., Heider, T., Floege, J., Holzman, L. B., Kriz, W., Moeller, M. J. (2007). Differentially Spliced Isoforms of FAT1 Are Asymmetrically Distributed within Migrating Cells. J. Biol. Chem. 282: 22823-22833 [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]  
  • Yanagida-Asanuma, E., Asanuma, K., Kim, K., Donnelly, M., Young Choi, H., Hyung Chang, J., Suetsugu, S., Tomino, Y., Takenawa, T., Faul, C., Mundel, P. (2007). Synaptopodin Protects Against Proteinuria by Disrupting Cdc42:IRSp53:Mena Signaling Complexes in Kidney Podocytes. Am. J. Pathol. 171: 415-427 [Abstract] [Full Text]  
  • Jefferson, J. A., Shankland, S. J. (2007). Familial nephrotic syndrome: PLCE1 enters the fray. Nephrol Dial Transplant 22: 1849-1852 [Full Text]  
  • Kaufman, L., Yang, G., Hayashi, K., Ashby, J. R., Huang, L., Ross, M. J., Klotman, M. E., Klotman, P. E. (2007). The homophilic adhesion molecule sidekick-1 contributes to augmented podocyte aggregation in HIV-associated nephropathy. FASEB J. 21: 1367-1375 [Abstract] [Full Text]  
  • Patrakka, J., Xiao, Z., Nukui, M., Takemoto, M., He, L., Oddsson, A., Perisic, L., Kaukinen, A., Szigyarto, C. A.-K., Uhlen, M., Jalanko, H., Betsholtz, C., Tryggvason, K. (2007). Expression and Subcellular Distribution of Novel Glomerulus-Associated Proteins Dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik. J. Am. Soc. Nephrol. 18: 689-697 [Abstract] [Full Text]  
  • Schmitz, C., Kinge, P., Hutter, H. (2007). Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc. Natl. Acad. Sci. USA 104: 834-839 [Abstract] [Full Text]  
  • Hou, R., Liu, L., Anees, S., Hiroyasu, S., Sibinga, N. E.S. (2006). The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals. JCB 173: 417-429 [Abstract] [Full Text]  
  • Tryggvason, K., Patrakka, J., Wartiovaara, J. (2006). Hereditary proteinuria syndromes and mechanisms of proteinuria.. NEJM 354: 1387-1401 [Full Text]  
  • Lehtonen, S., Ryan, J. J., Kudlicka, K., Iino, N., Zhou, H., Farquhar, M. G. (2005). Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and {alpha}-actinin are components of the nephrin multiprotein complex. Proc. Natl. Acad. Sci. USA 102: 9814-9819 [Abstract] [Full Text]  
  • Tanoue, T., Takeichi, M. (2005). New insights into Fat cadherins. J. Cell Sci. 118: 2347-2353 [Abstract] [Full Text]  
  • Tryggvason, K., Wartiovaara, J. (2005). How Does the Kidney Filter Plasma?. Physiology 20: 96-101 [Abstract] [Full Text]  
  • Reiser, J., Mundel, P. (2004). Danger Signaling by Glomerular Podocytes Defines a Novel Function of Inducible B7-1 in the Pathogenesis of Nephrotic Syndrome. J. Am. Soc. Nephrol. 15: 2246-2248 [Full Text]  
  • Reiser, J., Oh, J., Shirato, I., Asanuma, K., Hug, A., Mundel, T. M., Honey, K., Ishidoh, K., Kominami, E., Kreidberg, J. A., Tomino, Y., Mundel, P. (2004). Podocyte Migration during Nephrotic Syndrome Requires a Coordinated Interplay between Cathepsin L and {alpha}3 Integrin. J. Biol. Chem. 279: 34827-34832 [Abstract] [Full Text]  
  • Kojima, K., Davidovits, A., Poczewski, H., Langer, B., Uchida, S., Nagy-Bojarski, K., Hovorka, A., Sedivy, R., Kerjaschki, D. (2004). Podocyte Flattening and Disorder of Glomerular Basement Membrane Are Associated with Splitting of Dystroglycan-Matrix Interaction. J. Am. Soc. Nephrol. 15: 2079-2089 [Abstract] [Full Text]  
  • Matakatsu, H., Blair, S. S. (2004). Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development 131: 3785-3794 [Abstract] [Full Text]  
  • Castillejo-Lopez, C., Arias, W. M., Baumgartner, S. (2004). The fat-like Gene of Drosophila Is the True Orthologue of Vertebrate Fat Cadherins and Is Involved in the Formation of Tubular Organs. J. Biol. Chem. 279: 24034-24043 [Abstract] [Full Text]  
  • Benzing, T. (2004). Signaling at the Slit Diaphragm. J. Am. Soc. Nephrol. 15: 1382-1391 [Full Text]  
  • Tanoue, T., Takeichi, M. (2004). Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact. JCB 165: 517-528 [Abstract] [Full Text]  
  • Roselli, S., Heidet, L., Sich, M., Henger, A., Kretzler, M., Gubler, M.-C., Antignac, C. (2004). Early Glomerular Filtration Defect and Severe Renal Disease in Podocin-Deficient Mice. Mol. Cell. Biol. 24: 550-560 [Abstract] [Full Text]  
  • Huber, T. B., Simons, M., Hartleben, B., Sernetz, L., Schmidts, M., Gundlach, E., Saleem, M. A., Walz, G., Benzing, T. (2003). Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. Hum Mol Genet 12: 3397-3405 [Abstract] [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»