Animal models of primary biliary cirrhosis

Semin Liver Dis. 2014 Aug;34(3):285-96. doi: 10.1055/s-0034-1383728. Epub 2014 Jul 24.

Abstract

Within the last decade, several mouse models that manifest characteristic features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the authors discuss the current findings on two spontaneous (nonobese diabetic autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth factor-β receptor II [dnTGFβRII]) and two induced (chemical xenobiotics and microbial immunization) models of PBC. These models exhibit the serological, immunological, and histopathological features of human PBC. From these animal models, it is evident that the etiology of PBC is multifactorial and requires both specific genetic predispositions and environmental insults (either xenobiotic chemicals or microbial), which lead to the breaking of tolerance and eventually liver pathology. Human PBC is likely orchestrated by multiple factors and hence no single model can fully mimic the immunopathophysiology of human PBC. Nevertheless, knowledge gained from these models has greatly advanced our understanding of the major immunological pathways as well as the etiology of PBC.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • Bile Ducts, Intrahepatic / immunology*
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / microbiology
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers / blood
  • Disease Models, Animal*
  • Escherichia coli / pathogenicity
  • Humans
  • Liver Cirrhosis, Biliary / blood
  • Liver Cirrhosis, Biliary / chemically induced
  • Liver Cirrhosis, Biliary / genetics
  • Liver Cirrhosis, Biliary / immunology*
  • Liver Cirrhosis, Biliary / metabolism
  • Liver Cirrhosis, Biliary / microbiology
  • Liver Cirrhosis, Biliary / pathology
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Sphingomonadaceae / pathogenicity
  • Xenobiotics

Substances

  • Biomarkers
  • Receptors, Transforming Growth Factor beta
  • Xenobiotics
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II