| First Author | Golson ML | Year | 2009 |
| Journal | Gastroenterology | Volume | 136 |
| Issue | 5 | Pages | 1761-71.e1 |
| PubMed ID | 19208348 | Mgi Jnum | J:148722 |
| Mgi Id | MGI:3846276 | Doi | 10.1053/j.gastro.2009.01.040 |
| Citation | Golson ML, et al. (2009) Ductal malformation and pancreatitis in mice caused by conditional Jag1 deletion. Gastroenterology 136(5):1761-71.e1 |
| abstractText | BACKGROUND & AIMS: Alagille syndrome is an autosomal dominant disorder caused by mutations in Notch signaling pathway genes, usually JAGGED1. Up to 40% of Alagille syndrome patients also display exocrine pancreatic insufficiency, the pathobiology of which is unknown. Additionally, no mouse model recapitulating this aspect of the disease has been reported. METHODS: We conditionally deleted both alleles of Jagged1 in the murine pancreas using Cre-loxP technology and analyzed histologic and morphologic features in postnatal and adult pancreas such as duct structure, acinar mass, and T-lymphocyte infiltration, as well as markers of pancreatic function, including fecal fat. RESULTS: Jagged1-deficient mice displayed malformed pancreatic ducts with resulting acinar cell death, fatty infiltration of the parenchyma, fibrosis, pancreatitis, and pancreatic insufficiency. CONCLUSIONS: Pancreatic ductal malformation and acinar cell loss may be responsible for pancreatic insufficiency in Jagged1-deficient mice and, by corollary, in Alagille syndrome patients. |
