Animal models of primary biliary cirrhosis.

Abstract:

:Primary biliary cirrhosis (PBC) is characterized histologically by the presence of chronic non-suppurative destructive cholangitis of the small interlobular bile duct, leading to chronic progressive cholestasis. Most PBC patients are asymptomatic and have a reasonable prognosis, but a few develop esophageal varices or jaundice, rapidly leading to liver failure within a short period. As multiple factors appear to be involved in the onset of PBC, its clinical course may be complicated. Therefore, the use of an animal model would be valuable for clarifying the pathogenesis of PBC. Here, we review recent data of selected PBC models, particularly spontaneous models, xenobiotic immunized models, and infection-triggered models. There are a number of spontaneous models: the NOD.c3c4, dominant-negative TGF-β receptor II, IL-2Rα-/-, Scurfy, and Ae2a,b-/- mice. These animal models manifest distinct clinical and immunological features similar, but also often different, from those of human PBC. It is clear that a combination of genetic predisposition, environmental factors, and immunological dysfunction contribute to the pathogenesis of PBC. The diverse clinical course and complexity of the immunological mechanisms of PBC cannot be fully recapitulated solely any single animal model. The challenge remains to develop a progressive PBC disease model that exhibits fibrosis, and ultimately hepatic failure.

authors

Katsumi T,Tomita K,Leung PS,Yang GX,Gershwin ME,Ueno Y

doi

10.1007/s12016-015-8482-y

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

142-53

issue

2-3

eissn

1080-0549

issn

1559-0267

journal_volume

48

pub_type

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