Related Experiment Video
Updated: May 16, 2026
Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Published on: April 27, 2017
mTrop1/Epcam knockout mice develop congenital tufting enteropathy through dysregulation of intestinal
Emanuela Guerra1, Rossano Lattanzio, Rossana La Sorda
1Unit of Cancer Pathology, CeSI, University G. d'Annunzio Foundation, Chieti, Italy. emanuela.guerra5@gmail.com
Abstract:
Congenital tufting enteropathy (CTE) is a life-threatening hereditary disease that is characterized by enteric mucosa tufting degeneration and early onset, severe diarrhea. Loss-of-function mutations of the human EPCAM gene (TROP1, TACSTD1) have been indicated as the cause of CTE. However, loss of mTrop1/Epcam in mice appeared to lead to death in utero, due to placental malformation. This and indications of residual Trop-1/EpCAM expression in cases of CTE cast doubt on the role of mTrop1/Epcam in this disease. The aim of this study was to determine the role of TROP1/EPCAM in CTE and to generate an animal model of this disease for molecular investigation and therapy development. Using a rigorous gene-trapping approach, we obtained mTrop1/Epcam -null (knockout) mice. These were born alive, but failed to thrive, and died soon after birth because of hemorrhagic diarrhea. The intestine from the mTrop1/Epcam knockout mice showed intestinal tufts, villous atrophy and colon crypt hyperplasia, as in human CTE. No structural defects were detected in other organs. These results are consistent with TROP1/EPCAM loss being the cause of CTE, thus providing a viable animal model for this disease, and a benchmark for its pathogenetic course. In the affected enteric mucosa, E-cadherin and β-catenin were shown to be dysregulated, leading to disorganized transition from crypts to villi, with progressive loss of membrane localization and increasing intracellular accumulation, thus unraveling an essential role for Trop-1/EpCAM in the maintenance of intestinal architecture and functionality.Supporting information is available for this article.
Insights
Congenital tufting enteropathy (CTE) is caused by EPCAM gene mutations. This study generated a mouse model with CTE-like symptoms, confirming EPCAM
Area of Science:
- Genetics and Molecular Biology
- Gastroenterology
- Developmental Biology
Background:
- Congenital tufting enteropathy (CTE) is a severe inherited diarrheal disease.
- Loss-of-function mutations in the EPCAM gene are implicated in human CTE.
- Previous mouse models suggested EPCAM might not be the sole cause due to embryonic lethality.
Purpose of the Study:
- To clarify the role of EPCAM in CTE.
- To develop a viable animal model for CTE research and therapeutic development.
Main Methods:
- Utilized a gene-trapping approach to create EPCAM-null (knockout) mice.
- Observed and analyzed the phenotype of the resulting knockout mice.
- Examined intestinal tissue for structural and molecular changes.
Main Results:
- EPCAM-null mice exhibited symptoms mirroring human CTE, including intestinal tufting, villous atrophy, and diarrhea.
- These mice died shortly after birth due to hemorrhagic diarrhea.
- Dysregulation of E-cadherin and beta-catenin was observed in the enteric mucosa.
Conclusions:
- Loss of EPCAM function is directly causative of CTE.
- The generated mouse model is suitable for studying CTE pathogenesis and testing therapies.
- EPCAM is crucial for maintaining intestinal architecture and epithelial cell adhesion.
