A green light glows on copper disorders research

Abstract

The complete genome of Arabidopsis thaliana – the first from the plant kingdom – is now in our hands. Expectations are that this discovery will also benefit fields not directly related to plant genetics and crop production. Human health could be one of these fields. This hope is fueled by the discovery that many of the Arabidopsis genes show a significant similarity to genes involved in human disease syndromes. In some cases, the human genes are more similar to the Arabidopsis homologues than to the genes of yeast, Drosophila, or Caenorhabditis elegans. Included in this group are the genes implicated in Wilson's and Menkes diseases, two disorders of copper homeostasis [Nature (2000) 408, 823–826]. The defective functioning of the membrane-bound copper-transporting P-type ATPases that are coded by these genes, leads to copper deficiency (Menkes) or copper accumulation (Wilson). Of the two conditions, Menkes is by far the worst, being usually fatal in childhood. Researchers at Deakin University (Burwood, Victoria, Australia) led by Julian Mercer, together with colleagues from Melbourne University (Melbourne, Victoria, Australia), are studying Menkes protein structure and function, and trying to understand why different mutations of the Menkes gene give rise to the diverse aspects of the disease. Experimental efforts are also directed at understanding how deleterious Menkes effects can be over-run on a genetic and molecular level. Study strategies include the transfection of cells from Menkes patients with healthy Menkes genes, and the manipulation of the Wilson's gene (which is normal in Menkes patients), to act as a surrogate for the defective Menkes gene.