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- W2510752935 abstract "Congenital tufting enteropathy (CTE) is a devastating diarrheal disease seen in infancy associated with villous changes and the appearance of epithelial tufts. Sivagnanam et al., found mutations in epithelial cell adhesion molecule (EpCAM) to be the causative factor in CTE. We developed a knock-down cell model of CTE through transfection of an EpCAM shRNA construct into T84 cells to elucidate the in vitro role of EpCAM in barrier function and ion transport. Transfected cells exhibited decreased electrical resistance, increased permeability, and decreased ion transport as assessed through the use of western blotting, immunohistochemistry and Ussing chambers. An in vivo mouse model, based on a mutation found in CTE patients, was developed allowing for inducible deletion of exon 4 in Epcam resulting in a mutant protein with decreased expression. Tamoxifen- induced Epcam[Delta]⁴[Delta]⁴ mice demonstrated pathological features of villous atrophy, epithelial tufts and intracellular gaps, similar to human CTE patients, within four days post-induction. Epcam[Delta]⁴[Delta]⁴ mice also showed decreased expression of tight junctional proteins, increased permeability and decreased ion transport in the intestines. These findings, together with the knock-down model, reveal potential underlying disease mechanisms in CTE" @default.
- W2510752935 created "2016-09-16" @default.
- W2510752935 creator A5065877135 @default.
- W2510752935 date "2014-01-01" @default.
- W2510752935 modified "2023-09-27" @default.
- W2510752935 title "A deficiency in the congenital tufting enteropathy gene, EpCAM, results in intestinal barrier and ion transport dysfunction" @default.
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