Matriptase drives early-onset intestinal failure in a mouse model of congenital tufting enteropathy

摘要: Syndromic congenital tufting enteropathy (CTE) is a life-threatening recessive human genetic disorder that caused by mutations in SPINT2, encoding the protease inhibitor HAI-2, and characterized severe intestinal dysfunction. We recently reported generation of Spint2-deficient mouse model CTE. Here, we show CTE-associated early-onset failure lethality mice unchecked activity serine matriptase. Macroscopic histological defects observed absence including villous atrophy, luminal bleeding, loss mucin-producing goblet cells, defined crypt architecture resulting acute inflammatory response large intestine, were all prevented intestinal-specific inactivation St14 gene The cell junctional proteins EpCAM claudin 7 was also prevented. As result, matriptase allowed to gain weight after birth dramatically increased their lifespan. These data implicate as causative agent development CTE may provide new target for treatment individuals carrying SPINT2 mutations.This article has an associated 'The people behind papers' interview.