CCAAT/Enhancer binding protein alpha Knock-in mice exhibit early Liver glycogen storage, reduced susceptibility to hepatocellular carcinoma and increased hepatocyte functions

Abstract

The CCAAT/enhancer binding protein alpha (C/EBPa) is a transcription factor that is highly expressed in the liver and adipocytes. C/EBPa is a regulator that transactivates the transcription of many energy-related genes. C/EBPa also induces cellular growth arrest and terminal differentiation in hepatocytes and adipocytes. Our lab has created a C/EBPa knock-in mouse model where a single-copy of C/EBPa gene was placed under the regulation of one of the two endogenous alleles of the mouse alpha fetoprotein (AFP) gene promoter. This strategic placement of the C/EBPa knock-in gene under the regulatory control of the AFP promoter allows for the artificial expression of the C/EBPa during fetal development and during hepatocarcinogenesis, when the AFP promoter is active. Taken together, the data show that C/EBPa knock-in mice exhibit early glycogen storage and glycogen synthase expression as compared to wild type mice. C/EBPa knock-in mice are also more resistant to hepatocarcinogenesis. C/EBPa knock-in hepatocytes also exhibit enhanced albumin production.