Elevated copper impairs hepatic nuclear receptor function in Wilson’s disease

Wooton-Kee, Clavia Ruth; Jain, Ajay K.; Wagner, Martin; Grusak, Michael A.; Finegold, Milton J.; Lutsenko, Svetlana; Moore, David D.

doi:10.1172/jci78991

Cited by 71 publications

(78 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Parameters associated with fibrosis and inflammation were diminished in the treated Atp7b −/− mice, without removal of copper from liver parenchyma. A similar point was made in a recent study of farnesoid X receptor (FXR) and RXR in the Atp7b −/− mouse . Elevated copper concentrations were shown to interfere with binding of FXR and RXR to appropriate response elements.…”

supporting

confidence: 69%

Broadening the implications of gene discovery

Roberts

2016

Hepatology

View full text Add to dashboard Cite

supporting

confidence: 69%

Broadening the implications of gene discovery

Roberts

2016

Hepatology

View full text Add to dashboard Cite

“…; Wooton‐Kee et al . ). These abnormalities are also present in the liver of human WD patients (Hamilton et al .…”

Section: Rodent Modelsmentioning

confidence: 97%

“…; Wooton‐Kee et al . ). Furthermore, the abnormality in farnesoid X receptor function can be reversed in Atp7b −/− mice by the administration of zinc (Wooton‐Kee et al .…”

Section: Rodent Modelsmentioning

confidence: 97%

“…Furthermore, the abnormality in farnesoid X receptor function can be reversed in Atp7b −/− mice by the administration of zinc (Wooton‐Kee et al . ), while administration of an liver X receptor agonist can normalise lipid metabolism, decrease liver inflammation and fibrosis and improve liver function in Atp7b −/− mice (Hamilton et al . ).…”

Section: Rodent Modelsmentioning

confidence: 99%

See 1 more Smart Citation

Animal models of Wilson disease

Reed

Lutsenko²,

Bandmann

2018

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency.

show abstract

“…We have not yet been able to definitively show how copper disrupts LXR-mediated lipid metabolism in animals, but in vitro experiments have shown that copper can alter nuclear receptor signaling. (2) …”

mentioning

confidence: 99%