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Wilson Disease (Copper Toxicosis – CT) - Labrador Retriever Type
| Acronym: | CTOX-B |
| Gene: | ATP7B |
| Mutation: | c.4151G>A |
| Inheritance: | Autosomal Recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Copper Toxicosis (CT) also referred to as Wilson Disease is a complex genetic disorder found in Labrador retriever dogs characterized by a gradual accumulation of copper in the hepatocytes, a cell type found in the liver. Copper accumulation may result in chronic hepatitis and liver cirrhosis which is a life-threatening condition, not only in dogs but also in other animals and humans. There is no cure for copper-associated hepatitis, but it could be controlled by a low-copper diet during the early stage of the disease if it is detected early enough. Affected dogs often start to show signs of the disease in early adulthood and they include cerebral degeneration, connective tissue abnormalities, coarse hair, and a failure to thrive. In Labrador retriever dogs, copper toxicosis was shown to be associated with a mutation in the ATP7B gene. ATP7B is a copper transporting ATPase that plays a role in copper transportation and when mutated causes downregulation of copper absorption by the small intestinal and increases copper accumulation in the hepatocytes.
Cooper accumulation disease specific to Labrador Retriever dogs is inherited as an autosomal recessive trait, requiring two copies of the mutated ATP7B gene for the disease to develop. Dogs with only one copy of the mutated gene will not develop the disease but may act as carriers and pass the mutation to their offspring. Since the disease may have severe consequences, early detection by genetic testing is crucial for helping breeders in selecting future mating pairs and preventing the passing of the mutation to the offspring.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Fieten, H., Gill, Y., Martin, A. J., Concilli, M., Dirksen, K., van Steenbeek, F. G., Spee, B., van den Ingh, T. S., Martens, E. C., Festa, P., Chesi, G., van de Sluis, B., Houwen, R. H., Watson, A. L., Aulchenko, Y. S., Hodgkinson, V. L., Zhu, S., Petris, M. J., Polishchuk, R. S., Leegwater, P. A., … Rothuizen, J. (2016). The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders. Disease models & mechanisms, 9(1), 25–38. https://doi.org/10.1242/dmm.020263
Takanosu, M., Suzuki, K. (2022). Genotype frequency of ATP7A and ATP7B mutation-related copper-associated hepatitis in a Japanese guide dog Labrador retriever population. The Journal of veterinary medical science, 84(1), 16–19. https://doi.org/10.1292/jvms.21-0369
Wu, X., den Boer, E. R., Vos-Loohuis, M., Steenbeek, F., Monroe, G. R., Nijman, I. J., Leegwater, P., Fieten, H. (2020). Investigation of Genetic Modifiers of Copper Toxicosis in Labrador Retrievers. Life (Basel, Switzerland), 10(11), 266. https://doi.org/10.3390/life10110266