Alpha-fetoprotein gene regulation: lessons from transgenic mice

The mouse alpha-fetoprotein (AFP) gene provides an excellent model system to study developmental gene activation and different aspects of liver-specific transcriptional control. AFP is activated early in hepatogenesis, repressed post-natally, and can be reactivated during liver regeneration and in hepatocellular carcinomas. Transgenic studies have also revealed that AFP enhancers, when linked individually to a heterologous promoter, can confer zonal control in the adult liver. Continued transgenic studies, combined with analysis using in vitro and tissue culture systems, will help elucidate mechanisms of transcriptional regulation during liver development and hepatocarcinogenesis.