A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn; Holmberg, Dan

http://hdl.handle.net/10400.7/683

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Authors

Fransén-Pettersson, Nina

Schmidt-Christensen, Anja

Ivars, Fredrik

Abstract(s)

Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

Description

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Keywords

Mouse models Fibrosis Genetically modified animals Cytokines Inflammation T cells Inflammatory diseases Spleen

URI

http://hdl.handle.net/10400.7/683

Citation

Fransén-Pettersson N, Duarte N, Nilsson J, Lundholm M, Mayans S, Larefalk Å, et al. (2016) A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis. PLoS ONE 11(7): e0159850. doi:10.1371/journal.pone.0159850