Copper Toxicosis Bedlington Terrier Type (CT)
Copper Toxicosis Bedlington Terrier Type (CT) is a genetic disorder of copper accumulation unique to Bedlington terrier dog breed. Different hereditary forms of copper toxicosis have been identified in humans and dogs. In dogs, other than Bedlington Terriers, CT affected breeds are also West Highland White terrier, Skye terrier, Dalmatian, Dobermann and Labrador retriever. Human equivalent with similar phenotypes of this canine disorder are Menkes disease, Wilson’s disease, Indian childhood cirrhosis, endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis. CT in Bedlington Terrier was for first time described in the United States in the 1975 as a progressive form of chronic hepatitis followed by high liver copper levels. Soon after that chases in Australia and Europe have been documented.
In the body, copper can be found as a trace element, but in certain excess concentrations it can be highly toxic and therefore its concentrations are tightly regulated. Copper has an essential role in various biological processes, such as mitochondrial respiration, antioxidant defence, connective tissue formation, neurotransmitter synthesis, iron metabolism and pigmentation.
Copper is being absorbed in the small intestine via specific transporters. In the blood, it is found bound in complexes with small molecules, such as histidine and to serum proteins. In such form it will be transported to liver, its primary storage location.
There have been two copper carrier proteins identified, which have been connected with copper deficiency when defected.
Characteristics and Symptoms
Copper Toxicosis Bedlington Terrier Type (CT) is characterized by accumulation of cooper in the liver as a result of inefficient excretion of copper via the bile. This leads to chronic hepatitis and in most severe stage of the disease, cirrhosis. In first stage of the disease, clinical signs are present in the body of the dog but cannot be detected by any visual symptoms in the dog’s behaviour or external appearance. As the disorder progresses, hepatic necrosis (death of liver tissue) develops and first symptoms can be observed. These are lethargy, depression, anorexia, weight loss, vomiting, diarrhea, excessive thirst and urination, yellowish discoloration of skin, abnormalities in the stool and nervous system dysfunction. In Bedlington Terrier massive accumulation of copper in liver has been measured, highest that has been recognized in any dog breed. In one year old dogs measured copper levels were 2,000 µg/g dwl but with no presence of signs of hepatitis. Hepatitis occurs in affected dogs of 2-5 years of age and copper levels can reach values of 5,000 µg/g dwl, with extreme cases of 15,000 µg/g dwl
Copper Toxicosis Bedlington Terrier Type (CT) is caused by a mutation in COMMD1 gene (Copper Metabolism gene MURR1 containing Domain 1). The gene was originally named MURR1 gene, but upon discovery of nine other proteins related to the MURR1 protein, it was renamed into its current name. Prevalence of the mutation in the Bedlington Terrier breed is predicted to be high, ranging from 25 to 46% in different populations.
Genetic cause of CT in other breeds is unconfirmed and the mode of inheritance is unknown. CT in Bedlington Terrier is inherited in an autosomal recessive manner. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the copper toxicosis. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.