Maintaining normal levels of copper is important for growth, body function, and a healthy liver in dogs. Typically, copper is acquired through a dog’s diet and maintained at the correct level in the body by genes that can both raise and lower copper levels to maintain a balance known as homeostasis. Unfortunately, mutations in these genes can lead to high or low levels of copper that ultimately lead to health complications. Symptoms of the disease are typically observed between 2-7 years of age and can include neurologic issues, weight loss, jaundice, vomiting and a fluid filled abdomen. Affected dogs have issues removing excess copper from their liver which can build up and eventually lead to liver failure. For reasons we will explain in more detail, female dogs are impacted more than males. It is also important to note that diet can also combine with a genetic predisposition to contribute to the development of this disease. Copper Toxicosis can be definitively diagnosed by a veterinarian through a liver biopsy and copper level measurements. Through recent research, two of these mutations have been located and demonstrated to impact copper levels in the Labrador Retriever breed.
These two mutations exist in proteins known as ATP7A and ATP7B. ATP7A acts in the absorption of copper and ATP7B acts in the excretion of copper. Working together, these two genes maintain a balanced and appropriate level of copper in a dog’s body. Similar to humans, mutations in these genes can lead to either copper deficiency known as Menkes Disease or unhealthy copper accumulation known as Wilson’s Disease. Interestingly, different combinations of mutations in these two genes can actually have a neutralizing effect on changes in copper levels. This means that copper levels in Labrador Retrievers will depend on their mutation status for both genes.
Labrador Retrievers with a mutation in ATP7B but no mutation in ATP7A will very likely exhibit high copper levels. The ATP7B mutation acts in an additive way which means a dog with two copies of the mutation will have higher copper levels than a dog with one copy of the mutation. And dogs with one copy of the mutation will have higher copper levels than dogs with no copies of the mutation. Dogs that have one or two copies of the ATP7B mutation which increases copper levels can still have normal copper levels if the dog also has the ATP7A mutation which lowers copper levels back to normal.
The ability of ATP7A to lower copper levels is also dependent on whether the dog is male or female. Since the ATP7A gene and mutation exist on the X chromosome, males only have one copy of the gene which means the presence of the mutation in males has a very notable effect in lowering copper levels. Female dogs have two copies of the X chromosome which means they carry two copies of the ATP7A gene and require two copies of the mutation to see a notable effect. One copy of the ATP7A mutation will lower copper levels in females but not as much as two copies.
It is important to note that other breeds besides Labrador Retrievers can suffer from Copper Toxicosis. Research to date on Doberman Pinschers has detected and demonstrated a disease correlation for the ATP7B mutation but was unable to demonstrate the beneficial ATP7A mutation interaction with ATP7B in the breed. The ATP7B mutation has also been detected in other breeds like Black Russian Terriers and Bedlington Terriers that exhibit elevated copper levels. There appears to be an association with the ATP7B mutation in these breeds, however more research is needed to strengthen the association between the mutation and disease in these other breeds. An additional mutation in the COMMD1 gene was located in Bedlington Terriers that also appears to affect copper levels in the breed and it is likely that additional mutations may exist in other breeds leading to the same condition. Copper-associated liver diseases have been documented in other breeds like Dalmatians, West Highland White Terriers, Keeshonds and German Shepherds that lack both the ATP7A and ATP7B mutations.
It is important to know a Labrador Retriever’s genetic status for both the ATP7A and ATP7B mutations to make better informed breeding and health care decisions. It is recommended that any dogs determined to have either the ATP7A or ATP7B mutation be clinically evaluated by a veterinarian to determine copper levels that can then be managed by control of dietary copper intake. As always, don’t hesitate to contact us with any questions and together we can continue to promote the health of our canine companions.