Optimized Mouse Models for Liver Fibrosis

Methods Mol Biol. 2017:1559:279-296. doi: 10.1007/978-1-4939-6786-5_19.

Abstract

Fibrosis is the excessive accumulation of extracellular matrix components due to chronic injury, with collagens as predominant structural components. Liver fibrosis can progress to cirrhosis, which is characterized by a severe distortion of the delicate hepatic vascular architecture, the shunting of the blood supply away from hepatocytes and the resultant functional liver failure. Cirrhosis is associated with a highly increased morbidity and mortality and represents the major hard endpoint in clinical studies of chronic liver diseases. Moreover, cirrhosis is a strong cofactor of primary liver cancer. In vivo models are indispensable tools to study the cellular and molecular mechanisms of liver fibrosis and to develop specific antifibrotic therapies towards clinical translation. Here, we provide a detailed description of select optimized mouse models of liver fibrosis and state-of-the-art fibrosis readouts.

Keywords: Biliary fibrosis; Carbon tetrachloride (CCL4); Cirrhosis; Collagen; Extracellular matrix (ECM); Fibrosis; Hydroxyproline (HYP); Liver fibrosis; Mdr2-knockout; Metavir staging; Panlobular fibrosis; Picrosirius Red; Thioacetamide (TAA).

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / deficiency
  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP-Binding Cassette Sub-Family B Member 4
  • Animals
  • Azo Compounds / chemistry
  • Biomarkers / metabolism
  • Carbon Tetrachloride
  • Collagen / biosynthesis
  • Disease Models, Animal*
  • Disease Progression
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Gene Expression
  • Histocytochemistry / methods*
  • Humans
  • Hydroxyproline / biosynthesis
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Thioacetamide

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Azo Compounds
  • Biomarkers
  • Thioacetamide
  • C.I. direct red 80
  • Collagen
  • Carbon Tetrachloride
  • Hydroxyproline