TY - JOUR
T1 - Ductal Malformation and Pancreatitis in Mice Caused by Conditional Jag1 Deletion
AU - Golson, Maria L.
AU - Loomes, Kathleen M.
AU - Oakey, Rebecca
AU - Kaestner, Klaus H.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=65349177057&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65349177057&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2009.01.040
DO - 10.1053/j.gastro.2009.01.040
M3 - Article
C2 - 19208348
AN - SCOPUS:65349177057
VL - 136
SP - 1761-1771.e1
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 5
ER -