Liver fibrosis - Eskild

The Winnie Eskild group is working with a novel mouse model for liver fibrosis and lysosomal disorders.


About the group

The Winnie Eskild group is working with a novel mouse model for liver fibrosis and lysosomal disorders. It was created by ablation of kidney predominant protein, NCU-G1, a highly conserved protein with unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1gt/gt mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death.

We have demonstrated that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1gt/gt liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1gt/gt Kupffer cells. Furthermore, the Ncu-g1gt/gt mice have marked disturbances in their carbohydrate and lipid metabolism. Despite these ailments the Ncu-g1gt/gt mice grow well, are fertile and live at least till two years of age, however, at this age the majority have developed liver tumours. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we have proposed the Ncu-g1gt/gt mouse as a valuable new tool in the development of new treatments for the attenuation of fibrosis due to chronic liver damage.


Published Oct. 27, 2015 10:37 AM - Last modified July 12, 2022 10:50 PM


Group leader: 

Winnie Eskild