Kobbertoksikose (modifikator, ATP7A-relatert)

Copper levels in the body are regulated by both dietary intake and secretion from specific organs, such as the bile ducts. Multiple genes play crucial roles in maintaining optimal copper levels. A mutation in the ATP7B gene is associated with increased copper accumulation, leading to Wilson Disease, also called copper toxicosis or copper related hepatopathy. Conversely, mutations in modifier genes ATP7A or RETN appear to confer a protective effect against copper buildup in the liver, formerly known as Menkes Disease. Currently, these modifier genes are only relevant for Labrador Retrievers. However, the ATP7B mutation can cause clinical symptoms in several breeds. The ATP7B mutation has an incomplete dominant mode of inheritance. Dogs carrying one copy of the mutation have a somewhat increased risk of developing symptoms of copper toxicosis, while those affected with two copies have a much higher risk. This is because dysfunction of the ATP7B protein disrupts copper transport, potentially leading to liver cirrhosis. Symptom onset can be very subtle, and the age of onset varies between individuals, often 5-7 years of age. Disease severity is also influenced by dietary copper intake levels, and by genetic variants with a protective effect. In Labrador Retrievers, the a mutation in the gene ATP7A can mitigate copper levels, thereby reducing the risk and severity of Copper Toxicosis. Dogs carrying or affected by mutations in ATP7A are thus afforded some protection against copper toxicosis in the presence of an ATP7B mutation. The RETN mutation may be protective or neutral. The modifiers do not confer benefits in the absence of an ATP7B mutation. Consequently, testing Labradors and related breeds for all three mutations together is recommended.