title: How Useful Are Monogenic Rodent Models for the Study of Human Non-Alcoholic Fatty Liver Disease?
abstract: Improving understanding of the genetic basis of human non-alcoholic fatty liver disease (NAFLD) has the potential to facilitate risk stratification of affected patients, permit personalized treatment, and inform development of new therapeutic strategies. Animal models have been widely used to interrogate the pathophysiology of, and genetic predisposition to, NAFLD. Nevertheless, considerable interspecies differences in intermediary metabolism potentially limit the extent to which results can be extrapolated to humans. For example, human genome-wide association studies have identified polymorphisms in PNPLA3 and TM6SF2 as the two most prevalent determinants of susceptibility to NAFLD and its inflammatory component (NASH), but animal models of these mutations have had only variable success in recapitulating this link. In this review, we critically appraise selected murine monogenic models of NAFLD, NASH, and hepatocellular carcinoma (HCC) with a focus on how closely they mirror human disease.
authors.affiliation: Department of Paediatrics, University of Cambridge , Cambridge , UK.
authors.forename: Jake P
authors.initials: JP
authors.lastname: Mann
authors.affiliation: The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK; The National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Semple
authors.affiliation: Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK; Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Armstrong
keywords: animal model; genetic models; metabolic syndrome; steatohepatitis; steatosis