Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin

ML Hermiston, JI Gordon - Science, 1995 - science.org
ML Hermiston, JI Gordon
Science, 1995science.org
Cadherins mediate cell adhesion and are essential for normal development. Embryonic
stem cells were transfected with a dominant negative N-cadherin mutant (NCADΔ) 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
NCADΔ along the entire crypt-villus axis, but not in the villus epithelium alone, produced an
inflammatory bowel disease resembling Crohn's disease. NCADΔ perturbed proliferation …
Cadherins mediate cell adhesion and are essential for normal development. Embryonic stem cells were transfected with a dominant negative N-cadherin mutant (NCADΔ) 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 NCADΔ along the entire crypt-villus axis, but not in the villus epithelium alone, produced an inflammatory bowel disease resembling Crohn's disease. NCADΔ 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.
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