Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Liver and biliary tree formation involves the systematic expression of key transcriptional activators and signaling molecules by the endoderm as well as surrounding mesoderm. Control of early hepatic growth, the coordination of bile epithelial cell and hepatocyte differentiation that is necessary to generate a functioning liver and bile formation then occur with the regulated expression of a number of cytoskeletal, matrix and transport proteins. Mouse genetic studies, as well as in-vitro expiant culture studies have been pivotal to our present understanding of the many pathways involved in liver and biliary tree formation and function. Transgenic mice are an important tool for discovering the physiological function or the importance of certain proteins. Such mice, including knockout mice, are often generated by the disruption of a gene of interest. The process involves generating a construct that is made from genomic DNA fragment containing the essential part of the gene and replacing this with a selectable marker such as a Neo cassette.