| First Author | Szabo R | Year | 2019 |
| Journal | Development | Volume | 146 |
| Issue | 22 | PubMed ID | 31628112 |
| Mgi Jnum | J:284185 | Mgi Id | MGI:6390754 |
| Doi | 10.1242/dev.183392 | Citation | Szabo R, et al. (2019) Matriptase drives early-onset intestinal failure in a mouse model of congenital tufting enteropathy. Development 146(22):dev183392 |
| abstractText | Syndromic congenital tufting enteropathy (CTE) is a life-threatening recessive human genetic disorder that is caused by mutations in SPINT2, encoding the protease inhibitor HAI-2, and is characterized by severe intestinal dysfunction. We recently reported the generation of a Spint2-deficient mouse model of CTE. Here, we show that the CTE-associated early-onset intestinal failure and lethality of Spint2-deficient mice is caused by unchecked activity of the serine protease matriptase. Macroscopic and histological defects observed in the absence of HAI-2, including villous atrophy, luminal bleeding, loss of mucin-producing goblet cells, loss of defined crypt architecture and the resulting acute inflammatory response in the large intestine, were all prevented by intestinal-specific inactivation of the St14 gene encoding matriptase. The CTE-associated loss of the cell junctional proteins EpCAM and claudin 7 was also prevented. As a result, inactivation of intestinal matriptase allowed Spint2-deficient mice to gain weight after birth and dramatically increased their lifespan. These data implicate matriptase as a causative agent in the development of CTE and may provide a new target for the treatment of CTE in individuals carrying SPINT2 mutations.This article has an associated 'The people behind the papers' interview. |
