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

作者：Michelle L. Hermiston, Jeffrey I. Gordon · 发表于：Science · 年份：1995 · DOI：10.1126/science.270.5239.1203 · 被引用次数：670 · 研究领域：Wnt/β-catenin signaling in development and cancer、Cancer-related gene regulation、Kruppel-like factors research

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.