An autoimmune biliary disease mouse model for primary biliary cirrhosis: Something for everyone

Mason, Andrew L.

doi:10.1002/hep.21390

Cited by 16 publications

(18 citation statements)

References 30 publications

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“…20 Following the specific interaction of drug with HLA-B*57:01, the immune repertoire of endogenous peptides in the binding pocket is redirected, leading to activation of abacavirspecific T cells that drive polyclonal CD8 T-cell activation. 21 In the context of cholestasis, the HLA-B*57:01 association identified in a genome-wide association study for flucloxacillin-induced liver injury provides another example. 22 Intriguingly, while HLA is the strongest association for amoxicillin-clavulanate–induced liver injury, 23 variants in a classic autoimmune-related gene, PTPN22 , were also implicated.…”

Section: Heritability and The Role Of The Major Histocompatibility Comentioning

confidence: 99%

“…21 For PSC, histologic evidence of cholangitis or large duct disease has been induced by chemical cholangitis 77–80 or targeting of specific genes that alter the composition of bile. 81–86 The resultant pathology of genetic manipulation usually exemplifies other biliary processes, however, such as vanishing bile syndrome (Table 2).…”

Section: Animal Models Of Cholestasis Parallel Genomic Effortsmentioning

confidence: 99%

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The Genetics of Complex Cholestatic Disorders

et al. 2013

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Cholestatic liver diseases are caused by a range of hepatobiliary insults and involve complex interactions among environmental and genetic factors. Little is known about the pathogenic mechanisms of specific cholestatic diseases, which has limited our ability to manage patients with these disorders. However, recent genome-wide studies have provided insight into the pathogenesis of gallstones, primary biliary cirrhosis, and primary sclerosing cholangitis. A lithogenic variant in the gene that encodes the hepatobiliary transporter ABCG8 has been identified as a risk factor for gallstone disease; this variant has been associated with altered cholesterol excretion and metabolism. Other variants of genes encoding transporters that affect the composition of bile have been associated with cholestasis, namely ABCB11, which encodes the bile salt export pump, and ABCB4, which encodes hepatocanalicular phosphatidylcholine floppase. Many genes associated with gallstones have also been linked with vanishing bile duct syndromes and other cholestatic disorders. In contrast, studies have associated primary biliary cirrhosis and primary sclerosing cholangitis with genes encoding major histocompatibility complex proteins and identified loci associated with microbial sensing and immune regulatory pathways outside this region, such as genes encoding IL12, STAT4, IRF5, IL2 and its receptor (IL2R), CD28, and CD80. These discoveries have raised interest in the development of reagents that target these gene products. We review recent findings from genetic studies of patients with cholestatic liver disease. Future characterization of genetic variants in animal models, stratification of risk alleles by clinical course, and identification of interacting environmental factors will increase our understanding of these complex cholestatic diseases.

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Section: Heritability and The Role Of The Major Histocompatibility Comentioning

confidence: 99%

Section: Animal Models Of Cholestasis Parallel Genomic Effortsmentioning

confidence: 99%

The Genetics of Complex Cholestatic Disorders

et al. 2013

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“…Koarada et al described the NOD.c3c4 congenic mouse as the first spontaneous model for autoimmune biliary diseases [81, 82]. NOD.c3c4 mice develop lymphocytic peribiliary infiltrates, autoantibodies, and progressive cholestasis [81].…”

Section: Mouse Models That Mimic Specific Human Diseasesmentioning

confidence: 99%

Mouse Models of Liver Fibrosis Mimic Human Liver Fibrosis of Different Etiologies

et al. 2014

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The liver has the amazing capacity to repair itself after injury; however, the same processes that are involved in liver regeneration after acute injury can cause serious consequences during chronic liver injury. In an effort to repair damage, activated hepatic stellate cells trigger a cascade of events that lead to deposition and accumulation of extracellular matrix components causing the progressive replacement of the liver parenchyma by scar tissue, thus resulting in fibrosis. Although fibrosis occurs as a result of many chronic liver diseases, the molecular mechanisms involved depend on the underlying etiology. Since studying liver fibrosis in human subjects is complicated by many factors, mouse models of liver fibrosis that mimic the human conditions fill this void. This review summarizes the general mouse models of liver fibrosis and mouse models that mimic specific human disease conditions that result in liver fibrosis. Additionally, recent progress that has been made in understanding the molecular mechanisms involved in the fibrogenic processes of each of the human disease conditions is highlighted.

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“…AMA are rarely detected in humans and highly specific for PBC but appear to be commonly observed in spontaneous mouse models of PBC with immune deficits [6]. For example, the NOD.c3c4 mouse was derived from the non-obese diabetic (NOD) that has diverse innate and adaptive immune deficiencies [6].…”

Section: Introductionmentioning

confidence: 99%