Copper blues and the toxic mouse trap

Wilson's disease is a hereditary condition that causes copper to accumulate in tissues and leads to damage to the nervous system and liver. About one in a hundred people are carriers of the gene mutation but show no symptoms. However, atomic absorption spectroscopy of tissues from a mouse model of Wilson's disease has revealed that asymptomatic carriers are at increased susceptibility to copper overload when exposed to chronically high levels in their diet.

Katrina Allen of the Murdoch Children's Research Institute, at the University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia, and colleagues there and at Deakin University, Burwood, Victoria, and RMIT University, in Bundoora, Victoria, investigated the effect of chronic excess copper in drinking water on a mouse model. The specific mouse strain, which are carriers of a disease similar in effect to Wilson's disease mutation is known as the "toxic milk" (tx) mouse.

The team provided mice with drinking water containing 300 milligrams per litre of copper for 4-7, 8-11, 12-15, or 16-20 months. Mouse liver, spleen, kidney, and brain tissue were analysed using atomic absorption spectroscopy at the end of each period to determine copper concentration. The researchers also measured enzyme activity in the plasma for ceruloplasmin oxidase and overall liver condition.

They found that this level of chronic copper in the diet of the tx mice significantly increased liver copper in the tx heterozygous (carriers) and tx homozygous (symptomatic) mice. Non-tx mice were resistant to the toxic effects of the increased intake of copper.

As one would expect, copper loading had the worst effects on the symptomatic mice. Levels of copper deposition outside the liver, in the spleen and kidney, for instance, were absent in carriers and non-Wilson mice. The researchers point out that although liver condition in the Wilson's mice was markedly abnormal, there were no differences in the overall condition of the carriers and non-Wilson mice. Nevertheless, the tx carrier mice were shown to have a reduced ability to excrete excess copper, this, the researchers say indicates that, "half of the normal liver Atp7b copper transporter activity is insufficient to deal with large copper intakes."

Allen and her colleagues conclude, that "Wilson's disease carriers in the human population may be at increased risk of copper loading if chronically exposed to elevated copper in food or drinking water."
Recent independent research, shows that patients with low ceruloplasmin (a copper-transporting molecule) have increased rates of haemochromatosis because ceruloplasmin is an iron oxidase in the cell. At the time of writing, Allen told SpectroscopyNOW, "I am currently working on haemochromatosis in humans - a disease of iron overload - and am interested in the interaction between being homozygous for haemochromatosis and heterozygote for Wilson's disease."