Liver fibrosis constitutes a considerable health problem in the human population. In order to further understand the molecular mechanisms underlying liver fibrogenesis it is mandatory to generate genetic mouse models closely resembling human disease development and progression.
Stat5 is a transcription factor that plays a central role in liver physiology. By making use of the Cre/loxP system we have generated mice lacking Stat5 in the liver. These mice show a strong liver fibrosis phenotype in model for cholestasis. Mice show a dramatic increase of collagen deposition, disturbed liver architecture, liver necrosis, bile duct infarcts and bile duct proliferation. Gene expression analysis in these animals shows impairment of the Growth hormone-Stat5-IGF-1 axis. Interestingly, also liver cirrhosis in human patients is associated to growth hormone resistance and low levels of IGF-1, thus making this mouse model and attractive tool to contribute to the understanding of liver fibrogenesis and progression.
Left panel: control liver. Right panel: fibrotic liver
Starting with September 2013 this research is financially supported in part by the Austrian Science Fund (FWF) through stand-alone project "Growth hormone resistance and liver fibrosis" (P25599).