Hepatocarcinogenesis in transgenic mice

Transgenic mouse models of altered hepatic gene expression have provided a new set of tools with which to study the molecular genesis of normal and pathological liver growth. Previously identified carcinogenic genomic changes (such as oncogene activation) can be tested for their transforming potency in liver, and the contribution to liver growth of genetic changes of unknown significance (such as expression of a growth factor) can be directly measured in vivo. Highly novel approaches also have become possible because of the liver's unique regenerative capacity following injury: introduction of cells from another mouse's liver into young AL-uPA mice has resulted in reconstitution of up to 80% of recipient liver by donor cells (Rhim et al., 1994). Use of immunotolerant mice and human donor cells in this approach should allow creation of mice carrying human livers. Finally, by combining transgenic and embryonic stem cell technologies, the latter allowing selective mutation or inactivation of desired genes, we now have the means to begin to answer many of the critical questions regarding mechanisms of liver growth regulation in the intact animal.