Copper Toxicosis (ATP7A and ATP7B)

Copper levels in the body are regulated by copper intake from food and by copper secretion from certain parts of the body (the bile ducts). Two proteins, ATP7A and ATP7B, are responsible to maintain normal copper levels in the body. ATP7A is expressed in intestinal cells and transports copper to the liver where it is stored whereas ATP7B is expressed in liver cells but also in brain cells and secretes the copper into the bile ducts. A mutation in the ATP7A gene leads to a copper deficiency in the body, sometimes known as Menkes disease. A mutation in the ATP7B gene leads to copper accumulation in the body, which is called Wilson disease.

Labrador Retrievers with mutations in both genes can have varied copper levels depending upon the combination of the alleles and environmetal factors. Scientific research suggests that the ATP7A mutation mitigates the effect of the ATP7B mutation, partially protecting affected dogs from the effects of Wilson Disease.

The ATP7B mutation appears to be inherited as an incomplete dominant condition, and is associated with decreased ceruloplasminbound copper and increased non-ceruloplasmin-bound copper in the blood. Both carrier and affected dogs for this mutation are at increased risk of developing copper toxicosis. The risk is highest for affected dogs. A buildup of copper in the body can result in liver cirrhosis and neuronal degeneration with a variable age of onset. In addition, disease severity is also depending on the copper intake levels from the diet.

The ATP7A mutation is associated with a decrease in hepatic copper levels, suggesting that it provides protection against copper toxicosis in dogs homozygous or heterozygous for the ATP7B mutation.