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 Caruana, G.
Right arrow Articles by Bernstein, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Caruana, G.
Right arrow Articles by Bernstein, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2001, p. 1475-1483, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1475-1483.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Craniofacial Dysmorphogenesis Including Cleft Palate in Mice with an Insertional Mutation in the discs large Gene

Georgina Caruana1,* and Alan Bernstein1,2,3

Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5,1 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5S 1A1,2 and Canadian Institutes of Health Research, Ottawa, Ontario K1A 0W9,3 Canada

Received 19 September 2000/Returned for modification 30 October 2000/Accepted 28 November 2000

The discs large (Dlg) protein, or synapse-associated protein 97 (SAP97), is a member of the membrane-associated guanylate kinase family of multidomain scaffolding proteins which recruits transmembrane and signaling molecules to localized plasma membrane sites. Murine dlg is the homologue of the Drosophila dlg tumor suppressor gene. The loss of dlg function in Drosophila disrupts cellular growth control, apicobasal polarity, and cell adhesion of imaginal disc epithelial cells, resulting in embryonic lethality. In this study, we isolated a mutational insertion in the murine dlg locus by gene trapping in totipotent embryonic stem cells. This insertion results in a truncated protein product that contains the N-terminal three PSD-95/DLG/ZO-1 domains of Dlg fused to the LacZ reporter and subsequently lacks the src homology 3 (SH3), protein 4.1 binding, and guanylate kinase (GUK)-like domains. The Dlg-LacZ fusion protein is expressed in epithelial, mesenchymal, neuronal, endothelial, and hematopoietic cells during embryogenesis. Mice homozygous for the dlg mutation exhibit growth retardation in utero, have hypoplasia of the premaxilla and mandible, have a cleft secondary palate, and die perinatally. Consistent with this phenotype, Dlg-LacZ is expressed in mesenchymal and epithelial cells throughout palatal development. Our genetic and phenotypic analysis of dlg mutant mice suggests that protein-protein interactions involving the SH3, protein 4.1 binding, and/or GUK-like domains are essential to the normal function of murine Dlg within craniofacial and palatal morphogenesis.

* Corresponding author. Present address: Department of Anatomy and Cell Biology, Monash University, Clayton Campus, Bldg. 13C, West Ring Rd., Victoria 3168, Australia. Phone: 61-3-9905-2751. Fax: 61-3-9905-2766. E-mail: g.caruana{at}med.monash.edu.au.

Molecular and Cellular Biology, March 2001, p. 1475-1483, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1475-1483.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Turgeon, B., Meloche, S. (2009). Interpreting Neonatal Lethal Phenotypes in Mouse Mutants: Insights Into Gene Function and Human Diseases. Physiol. Rev. 89: 1-26 [Abstract] [Full Text]  
  • Narayan, N., Massimi, P., Banks, L. (2009). CDK phosphorylation of the discs large tumour suppressor controls its localisation and stability. J. Cell Sci. 122: 65-74 [Abstract] [Full Text]  
  • Zhou, W., Zhang, L., Guoxiang, X., Mojsilovic-Petrovic, J., Takamaya, K., Sattler, R., Huganir, R., Kalb, R. (2008). GluR1 Controls Dendrite Growth through Its Binding Partner, SAP97. J. Neurosci. 28: 10220-10233 [Abstract] [Full Text]  
  • Lockwood, C. A., Lynch, A. M., Hardin, J. (2008). Dynamic analysis identifies novel roles for DLG-1 subdomains in AJM-1 recruitment and LET-413-dependent apical focusing. J. Cell Sci. 121: 1477-1487 [Abstract] [Full Text]  
  • Mendoza-Topaz, C., Urra, F., Barria, R., Albornoz, V., Ugalde, D., Thomas, U., Gundelfinger, E. D., Delgado, R., Kukuljan, M., Sanxaridis, P. D., Tsunoda, S., Ceriani, M. F., Budnik, V., Sierralta, J. (2008). DLGS97/SAP97 Is Developmentally Upregulated and Is Required for Complex Adult Behaviors and Synapse Morphology and Function. J. Neurosci. 28: 304-314 [Abstract] [Full Text]  
  • Iizuka-Kogo, A., Ishidao, T., Akiyama, T., Senda, T. (2007). Abnormal development of urogenital organs in Dlgh1-deficient mice. Development 134: 1799-1807 [Abstract] [Full Text]  
  • Bohl, J., Brimer, N., Lyons, C., Vande Pol, S. B. (2007). The Stardust Family Protein MPP7 Forms a Tripartite Complex with LIN7 and DLG1 That Regulates the Stability and Localization of DLG1 to Cell Junctions. J. Biol. Chem. 282: 9392-9400 [Abstract] [Full Text]  
  • Atasoy, D., Schoch, S., Ho, A., Nadasy, K. A., Liu, X., Zhang, W., Mukherjee, K., Nosyreva, E. D., Fernandez-Chacon, R., Missler, M., Kavalali, E. T., Sudhof, T. C. (2007). Deletion of CASK in mice is lethal and impairs synaptic function. Proc. Natl. Acad. Sci. USA 104: 2525-2530 [Abstract] [Full Text]  
  • Mahoney, Z. X., Sammut, B., Xavier, R. J., Cunningham, J., Go, G., Brim, K. L., Stappenbeck, T. S., Miner, J. H., Swat, W. (2006). Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Proc. Natl. Acad. Sci. USA 103: 19872-19877 [Abstract] [Full Text]  
  • Simonson, S. J.S., Difilippantonio, M. J., Lambert, P. F. (2005). Two Distinct Activities Contribute to Human Papillomavirus 16 E6's Oncogenic Potential. Cancer Res. 65: 8266-8273 [Abstract] [Full Text]  
  • Zordan, M. A., Massironi, M., Ducato, M. G., te Kronnie, G., Costa, R., Reggiani, C., Chagneau, C., Martin, J.-R., Megighian, A. (2005). Drosophila CAKI/CMG Protein, a Homolog of Human CASK, Is Essential for Regulation of Neurotransmitter Vesicle Release. J. Neurophysiol. 94: 1074-1083 [Abstract] [Full Text]  
  • Palmer, C. L., Cotton, L., Henley, J. M. (2005). The Molecular Pharmacology and Cell Biology of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors. Pharmacol. Rev. 57: 253-277 [Abstract] [Full Text]  
  • Bilder, D. (2004). Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors. Genes Dev. 18: 1909-1925 [Abstract] [Full Text]  
  • Leonoudakis, D., Conti, L. R., Anderson, S., Radeke, C. M., McGuire, L. M. M., Adams, M. E., Froehner, S. C., Yates, J. R. III, Vandenberg, C. A. (2004). Protein Trafficking and Anchoring Complexes Revealed by Proteomic Analysis of Inward Rectifier Potassium Channel (Kir2.x)-associated Proteins. J. Biol. Chem. 279: 22331-22346 [Abstract] [Full Text]  
  • Cox, E. A., Hardin, J. (2004). Sticky worms: adhesion complexes in C. elegans. J. Cell Sci. 117: 1885-1897 [Abstract] [Full Text]  
  • Fuja, T. J., Lin, F., Osann, K. E., Bryant, P. J. (2004). Somatic Mutations and Altered Expression of the Candidate Tumor Suppressors CSNK1{epsilon}, DLG1, and EDD/hHYD in Mammary Ductal Carcinoma. Cancer Res. 64: 942-951 [Abstract] [Full Text]  
  • Nguyen, M. M., Nguyen, M. L., Caruana, G., Bernstein, A., Lambert, P. F., Griep, A. E. (2003). Requirement of PDZ-Containing Proteins for Cell Cycle Regulation and Differentiation in the Mouse Lens Epithelium. Mol. Cell. Biol. 23: 8970-8981 [Abstract] [Full Text]  
  • Mantovani, F., Banks, L. (2003). Regulation of the Discs Large Tumor Suppressor by a Phosphorylation-dependent Interaction with the {beta}-TrCP Ubiquitin Ligase Receptor. J. Biol. Chem. 278: 42477-42486 [Abstract] [Full Text]  
  • Nguyen, M. L., Nguyen, M. M., Lee, D., Griep, A. E., Lambert, P. F. (2003). The PDZ Ligand Domain of the Human Papillomavirus Type 16 E6 Protein Is Required for E6's Induction of Epithelial Hyperplasia In Vivo. J. Virol. 77: 6957-6964 [Abstract] [Full Text]  
  • Chetkovich, D. M., Bunn, R. C., Kuo, S.-H., Kawasaki, Y., Kohwi, M., Bredt, D. S. (2002). Postsynaptic Targeting of Alternative Postsynaptic Density-95 Isoforms by Distinct Mechanisms. J. Neurosci. 22: 6415-6425 [Abstract] [Full Text]  
  • Lee, S., Fan, S., Makarova, O., Straight, S., Margolis, B. (2002). A Novel and Conserved Protein-Protein Interaction Domain of Mammalian Lin-2/CASK Binds and Recruits SAP97 to the Lateral Surface of Epithelia. Mol. Cell. Biol. 22: 1778-1791 [Abstract] [Full Text]  
  • Li, Y., Spangenberg, O., Paarmann, I., Konrad, M., Lavie, A. (2002). Structural Basis for Nucleotide-dependent Regulation of Membrane-associated Guanylate Kinase-like Domains. J. Biol. Chem. 277: 4159-4165 [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»