Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin.
Cadherins mediate cell adhesion and are essential for normal development. Embryonic stem cells were transfected with a dominant negative N-cadherin mutant (NCAD delta) 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 NCAD delta along the entire crypt-villus axis, but not in the villus epithelium alone, produced an inflammatory bowel disease resembling Crohn's disease. NCAD delta 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.
Hermiston
M L
ML
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gordon
J I
JI
D000236:Adenoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002678:Chimera; D003424:Crohn Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D007583:Jejunum / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D013234:Stem Cells; D014162:Transfection
D015820:Cadherins