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Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1254-1261. doi: 10.1016/j.bbadis.2017.06.027. Epub 2017 Jul 11.

Animal models of biliary injury and altered bile acid metabolism.

Author information

1
Department of Molecular Medicine, University of Padua, Padua, Italy.
2
Section of Digestive Disease, Liver Center, Yale University, Yale, USA.
3
Department of Molecular Medicine, University of Padua, Padua, Italy; Section of Digestive Disease, Liver Center, Yale University, Yale, USA. Electronic address: luca.fabris@unipd.it.
4
Institute of Pathology, University of Greifswald, Greifswald, Germany. Electronic address: diego.calvisi@uni-greifswald.de.

Abstract

In the last 25years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed. Overall, they have led to a range of liver phenotypes recapitulating the main features of biliary injury and altered bile acid metabolisms, such as ductular reaction, peribiliary inflammation and fibrosis, obstructive cholestasis and biliary dysgenesis. Although with a limited translability to the human setting, these mouse models have provided us with the ability to probe over time the fundamental mechanisms promoting cholestatic disease progression. Moreover, recent studies from genetically engineered mice have unveiled 'core' pathways that make the cholangiocyte a pivotal player in liver repair. In this review, we will highlight the main phenotypic features, the more interesting peculiarities and the different drawbacks of these mouse models. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

KEYWORDS:

Altered bile acid metabolism; Biliary injury; Cholangiocyte; Experimental models

PMID:
28709963
PMCID:
PMC5764833
DOI:
10.1016/j.bbadis.2017.06.027
[Indexed for MEDLINE]
Free PMC Article

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