title: Correction of the copper transport defect of Menkes patient fibroblasts by expression of two forms of the sheep Wilson ATPase.
abstract: The Wilson disease (WD) protein (ATP7B) is a copper-transporting P-type ATPase that is responsible for the efflux of hepatic copper into the bile, a process that is essential for copper homeostasis in mammals. Compared with other mammals, sheep have a variant copper phenotype and do not efficiently excrete copper via the bile, often resulting in excessive copper accumulation in the liver. To investigate the function of sheep ATP7B and its potential role in the copper-accumulation phenotype, cDNAs encoding the two forms of ovine ATP7B were transfected into immortalised fibroblast cell lines derived from a Menkes disease patient and a normal control. Both forms of ATP7B were able to correct the copper-retention phenotype of the Menkes cell line, demonstrating each to be functional copper-transporting molecules and suggesting that the accumulation of copper in the sheep liver is not due to a defect in the copper transport function of either form of sATP7B.
authors.affiliation: Center for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Building L, Burwood Campus, 221 Burwood Highway, Victoria 3125, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lockhart
authors.forename: Sharon
authors.initials: S
authors.lastname: La Fontaine
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Firth
authors.forename: Mark
authors.initials: M
authors.lastname: Greenough
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
authors.forename: Julian F B
authors.initials: JF
authors.lastname: Mercer
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D003301:Copper Radioisotopes; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D005347:Fibroblasts; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D012756:Sheep; D014162:Transfection
chemical_list: D027682:Cation Transport Proteins; D003301:Copper Radioisotopes; D000079923:Copper Transporter 1; D008565:Membrane Proteins; C490079:SLC31A1 protein, human; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases