Related Experiment Video
Updated: May 4, 2026
15:13
Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Published on: April 27, 2017
10.7K
Functional consequences of EpCam mutation in mice and men
James L Mueller1, Matthew D McGeough, Carla A Peña
1Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California San Diego, La Jolla, California;
American Journal of Physiology. Gastrointestinal and Liver Physiology
|December 17, 2013
Summary
Congenital tufting enteropathy (CTE) is a severe infant diarrheal disease. A new mouse model reveals EpCAM mutations disrupt the EpCAM/claudin-7 complex, causing intestinal barrier defects and disease.
Area of Science:
- Gastroenterology
- Molecular Biology
- Developmental Biology
Background:
- Congenital tufting enteropathy (CTE) is a severe infantile diarrheal disease.
- Mutations in the epithelial cell adhesion molecule (EpCAM) have been identified as the cause of CTE.
- Understanding the in vivo role of EpCAM is crucial for CTE pathogenesis.
Purpose of the Study:
- To develop and characterize a novel mouse model of CTE.
- To elucidate the in vivo function of EpCAM in intestinal homeostasis.
- To compare pathological features between the mouse model and human CTE patients.
Main Methods:
- Generation of Epcam exon 4 deletion (Epcam(Δ4/Δ4)) mouse model using Cre-LoxP technology.
- Histological analysis (light and electron microscopy) of intestinal tissue integrity.
- Immunohistochemistry to assess EpCAM and claudin-7 expression and colocalization.
Main Results:
- Epcam(Δ4/Δ4) mice exhibit neonatal lethality, growth retardation, and CTE-like pathology.
- Mutant EpCAM is present at low levels and mislocalized in mice and human CTE patients.
- Epcam deletion reduces EpCAM and claudin-7 expression, disrupting their complex and increasing intestinal permeability.
Conclusions:
- The Epcam(Δ4/Δ4) mouse model accurately recapitulates human CTE.
- Disruption of the EpCAM/claudin-7 complex is a key mechanism in CTE.
- This study provides insights into CTE pathogenesis and potential therapeutic targets.
