The Drosophila ATP7 copper transporter has sequence homology to the human copper transporters ATP7A and ATP7B, which are defective in Menkes and Wilson disease, respectively.
OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q), but also viability of Cu-treated human glioblastoma U87 cells.
After cloning of ATP7B, the spectrum of mutations and their clinical consequences have been investigated in patients with WD in different ethnic populations.
The present study focuses on the structural mitochondrial alterations that precede clinical symptoms in the livers of rats lacking Atp7b, an animal model for WD.
Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of female Long-Evans Cinnamon rats, a model of Wilson disease.
The gene responsible for WD is located in 13q14.3 chromosome, contains 21 exons and codes for copper specific transporting P-type adenosinetriphosphatase (ATPase) (ATP7B).
By utilizing the age at onset, neurological involvement score and ATP7B mutation background, we generated a genotype-phenotype matrix that could be effectively used to depict the phenotypic spectra of WD affected individuals and serve as a platform to identify prospective "outliers" to be investigated for their remarkable phenotypic divergence.
The genes for two copper-transporting ATPases, ATP7A and ATP7B, are defective in the heritable disorders of copper imbalance, Menkes disease (MNK) and Wilson disease (WND), respectively.
These examples illustrate how impaired regulation of copper transport pathways can cause organ damage and provide important insights into the impact of defects in specific molecular processes, including those catalyzed by the copper-transporting ATPases, ATP7A (mutated in Menkes disease), ATP7B (Wilson's disease), and the copper chaperones such as those for cytochrome c oxidase, SCO1 and SCO2.
Glutathione-S-transferase pull-down experiments, co-immunoprecipitations, immunofluorescence microscopy, site-directed mutagenesis, and biosynthetic labeling experiments were performed to characterize the interaction between COMMD1 and ATP7B and the effects of WD causing mutations.
Cu chelators and zinc salts are the two most important drugs used in the treatment of WD patients; however, the molecular mechanisms of the drugs with regard to ATP7B expression have not been determined.