Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition; Orlando, October 22-24, 1998
HEPATIC JAGGED1 EXPRESSION
Background: Mutations in Jagged1 have been shown to result in the Alagille syndrome, but the link between haploinsufficency of Jagged1 and intrahehpatic ductal paucity is unknown. This study of the expression of Jagged1 in liver was undertaken to determine the range of Jagged1 expression in fetal and post natal liver. Our results are the first demonstration of Jagged1 expression in postnatal rat and human liver specimens, and we localize the expression by immunohistochemistry to the biliary epithelium.
Methods: RT PCR primers were constructed for both rat and human Jagged1 mRNA sequences. Total RNA samples from human liver explants and normal rat livers at various stages of fetal and postnatal development were subjected to RT PCR. Immunohistochemistry was performed with a rabbit polyclonal antibody on fixed rat and human liver specimens.
Results: RT PCR demonstrates Jagged1 expression in all samples studied including rat liver embryonic days 16-21, 1 day old, 1 week old and 2 month old adult rats, and all time points in adult rat liver post bile duct ligation. RT PCR detected Jagged1 in total liver RNA extracted from every human sample tested. Human samples included cadaver organ donor samples from reduced human cadaver grafts and explanted native livers from pediatric patients with biliary atresia, fulminant hepatic failure, biliary atresia, tyrosinemia and chronic rejection. Immunohistochemistry of adult rat liver samples revealed staining of non-parenchymal cells in the sinusoids, most likely Kupffer cells, and the biliary epithelium. Immunohistochemistry of human liver tissue localized Jagged1 protein expression to the biliary epithelium. Additional studies of human fetal liver and various human diseases are underway.
Conclusions: Jagged1 is expressed in fetal and post natal liver in health and disease and is localized to non-parenchymal cells and to the biliary epithelium. Further Jagged1 studies will likely elucidate mechanisms of biliary epithelial regulation.
PLENARY SESSION III© 1998 Lippincott Williams & Wilkins, Inc.