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Science 17 November 1995:
Vol. 270. no. 5239, pp. 1203 - 1207
DOI: 10.1126/science.270.5239.1203
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Reports

Inflammatory Bowel Disease and Adenomas in Mice Expressing a Dominant Negative N-Cadherin

Michelle L. Hermiston and Jeffrey I. Gordon (1)

Cadherins mediate cell adhesion and are essential for normal development. Embryonic stem cells were transfected with a dominant negative N-cadherin mutant (NCADDelta) under the control of promoters active in small intestinal epithelial cells and then introduced into C57BL/6 mouse blastocysts. Analysis of adult chimeric mice revealed that expression of NCADDelta along the entire crypt-villus axis, but not in the villus epithelium alone, produced an inflammatory bowel disease resembling Crohn's disease. NCADDelta perturbed proliferation, migration, and death programs in crypts, which lead to adenomas. This model provides insights about cadherin function in an adult organ and the factors underlying inflammatory bowel disease and intestinal neoplasia.


Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
(1) To whom correspondence should be addressed.


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B. Romagnolo, D. Berrebi, S. Saadi-Keddoucci, A. Porteu, A.-l. Pichard, M. Peuchmaur, A. Vandewalle, A. Kahn, and C. Perret (1999)
Cancer Res. 59, 3875-3879
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III. The mucosal antigen barrier: cross talk with mucosal cytokines.
M. H. Perdue (1999)
Am J Physiol Gastrointest Liver Physiol 277, G1-G5
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The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues.
E. Pötter, C. Bergwitz, and G. Brabant (1999)
Endocr. Rev. 20, 207-239
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Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat.
J. B. Meddings, J. Jarand, S. J. Urbanski, J. Hardin, and D. G. Gall (1999)
Am J Physiol Gastrointest Liver Physiol 276, G951-G957
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Evaluation of 5-Aminosalicylic Acid (5-ASA) for Cancer Chemoprevention: Lack of Efficacy against Nascent Adenomatous Polyps in the ApcMin Mouse.
S. R. Ritland, J. A. Leighton, R. E. Hirsch, J. D. Morrow, A. L. Weaver, and S. J. Gendler (1999)
Clin. Cancer Res. 5, 855-863
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Colitis-Inducing Potency of CD4+ T Cells in Immunodeficient, Adoptive Hosts Depends on Their State of Activation, IL-12 Responsiveness, and CD45RB Surface Phenotype.
M. H. Claesson, S. Bregenholt, K. Bonhagen, S. Thoma, P. Moller, M. J. Grusby, F. Leithauser, M. H. Nissen, and J. Reimann (1999)
J. Immunol. 162, 3702-3710
   Abstract »    Full Text »    PDF »
Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats.
J M Mariadason, A Catto-Smith, and P R Gibson (1999)
Gut 44, 394-399
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Mechanism of extracellular domain-deleted dominant negative cadherins.
M. Nieman, J. Kim, K. Johnson, and M. Wheelock (1999)
J. Cell Sci. 112, 1621-1632
   Abstract »    PDF »
Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?.
J D Soderholm, G Olaison, E Lindberg, U Hannestad, A Vindels, C Tysk, G Jarnerot, and R Sjodahl (1999)
Gut 44, 96-100
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The Role of IL-10 in Inflammatory Bowel Disease: "Of Mice and Men".
M. W. Leach, N. J. Davidson, M. M. Fort, F. Powrie, and D. M. Rennick (1999)
Toxicol Pathol 27, 123-133
   Abstract »    PDF »
Oral tolerance in disease.
P GARSIDE, A M. MOWAT, and A KHORUTS (1999)
Gut 44, 137-142
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A Novel Model of Inflammatory Bowel Disease: Mice Deficient for the Multiple Drug Resistance Gene, mdr1a, Spontaneously Develop Colitis.
C. M. Panwala, J. C. Jones, and J. L. Viney (1998)
J. Immunol. 161, 5733-5744
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Modulation of Epithelial Cell Adhesion in Gastrointestinal Homeostasis.
J. A. Efstathiou and M. Pignatelli (1998)
Am. J. Pathol. 153, 341-347
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E-Cadherin-dependent Growth Suppression is Mediated by the Cyclin-dependent Kinase Inhibitor p27KIP1.
B. St. Croix, C. Sheehan, J. W. Rak, V. A. Florenes, J. M. Slingerland, and R. S. Kerbel (1998)
J. Cell Biol. 142, 557-571
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Effects of Forced Expression of an NH2-terminal Truncated {beta}-Catenin on Mouse Intestinal Epithelial Homeostasis.
M. H. Wong, B. Rubinfeld, and J. I. Gordon (1998)
J. Cell Biol. 141, 765-777
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Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.
J. A. Efstathiou, M. Noda, A. Rowan, C. Dixon, R. Chinery, A. Jawhari, T. Hattori, N. A. Wright, W. F. Bodmer, and M. Pignatelli (1998)
PNAS 95, 3122-3127
   Abstract »    Full Text »    PDF »
Direct and Regulated Interaction of Integrin {alpha}E{beta}7 with E-Cadherin.
J. M.G. Higgins, D. A. Mandlebrot, S. K. Shaw, G. J. Russell, E. A. Murphy, Y.-T. Chen, W. J. Nelson, C. M. Parker, and M. B. Brenner (1998)
J. Cell Biol. 140, 197-210
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