{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:33:28Z","timestamp":1790728408199,"version":"4.1.0"},"reference-count":51,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Syndromic congenital tufting enteropathy (CTE) is a life-threatening recessive human genetic disorder, which 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 life span. These data implicate matriptase as a causative agent in development of CTE and may provide a new target for the treatment of CTE in patients carrying SPINT2 mutations.<\/jats:p>","DOI":"10.1242\/dev.183392","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T16:37:50Z","timestamp":1571416670000},"source":"Crossref","is-referenced-by-count":23,"title":["Matriptase drives early-onset intestinal failure in a mouse model of congenital tufting enteropathy"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7661-8718","authenticated-orcid":false,"given":"Roman","family":"Szabo","sequence":"first","affiliation":[{"name":"Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LuLu K.","family":"Callies","sequence":"additional","affiliation":[{"name":"Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-4060","authenticated-orcid":false,"given":"Thomas H.","family":"Bugge","sequence":"additional","affiliation":[{"name":"Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"2021042623010673100_DEV183392C1","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/jid.2008.311","article-title":"Ichthyosis, follicular atrophoderma, and hypotrichosis caused by mutations in ST14 is associated with impaired profilaggrin processing","volume":"129","author":"Alef","year":"2009","journal-title":"J. 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