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- Title
Functional analysis of variants of the Wilson disease copper transporter, ATP7B.
- Authors
Benusic, Michael A.; Macintyre, Georgina; Cox, Diane W.
- Abstract
Copper is an essential trace element, acting as a cofactor for numerous enzymes that catalyze a multitude of biological processes. However, copper is toxic in excess. Wilson disease (WND) is an autosomal recessive disorder of copper homeostasis characterized by impaired biliary copper efflux. Copper accumulates in the liver, brain, and kidney, damaging these organs. Phenotypic manifestations of WND are highly variable, hampering many clinical and biochemical diagnostic methods. The WND gene, ATP7B, encodes a membrane ATPase which functions in transporting copper to apo-enzymes and trafficking excess copper out of cells. More than 500 variants have been identified in patients; functional analysis is crucial in determining if these are in fact disease-causing as opposed to rare normal variants. We use several assays to analyze the consequences of ATP7B variants: a transport assay within yeast, and trafficking and viability assays within a mammalian cell model. Ccc2p, a yeast homologue of ATP7B, delivers copper to Fet3p which is essential for growth under iron-limited conditions.
- Subjects
HEPATOLENTICULAR degeneration; FUNCTIONAL analysis; BIOLOGICAL transport; COPPER in the body; COPPER bioaccumulation
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p34
- ISSN
1920-7425
- Publication type
Abstract