7 Menkes and Wilson Diseases

Abstract

Publisher Summary This chapter discusses the clinical aspects of Menkes and Wilson diseases,the steps of positional cloning are presented to isolate and characterize the genes responsible for each disease, and animal models which have been implicated. The molecular understanding of Menkes and Wilson disease genes by positional cloning has unraveled an interesting new family of human copper transporters of the P-type ATPase. Although only two have been isolated, there could possibly be many more that are involved in the transport of other heavy metals besides copper as seen in bacteria. In Saccharomyces cerevisiae, a plasma membrane copper transporter has been isolated and a yeast copper-transporting P-type ATPase (ccc2) homologous to the human Menkes and Wilson diseases has been identified. These yeast genes should be important for understanding the functional relationship of the various proteins involved in copper transport across the plasma membrane and within the cell. Recently, the Menkes–Wilson disease gene homology in yeast (ccc2) has been shown to be required for the export of copper from the cytosol into an extracytosolic compartment, and ccc2 provides copper to a ceruloplasmin-like oxidase required for iron uptake.