Inherited Copper Toxicity of the Liver in Bedlington Terriers

Abstract

Breeders of Bedlington terriers have long suspected that a small number of their dogs were susceptible to fatal liver disease. Interest in this disorder increased sharply when the responses to a questionnaire circulated by the Bedlington Terrier Club of America revealed two facts: the incidence of the disorder was considerably higher than had been generally assumed, and although no environmental differences were evident, only some strains of Bedlingtons seemed to be afflicted, suggesting an etiological genetic factor. Hardy, Stevens & Stowe (1975) were impressed by the hobnailed gross appearance and the abundance of intra-hepatocytic brown pigment granules in the livers of 2 autopsied terriers. These findings, and the possibility that the disorder was hereditary, suggested to them that they might be dealing with a canine form of Wilson's disease. Sections of both dogs' livers stained with rubeanic acid were strongly positive for copper in the hepatocellular granules. We have extended the findings of Hardy, Stevens & Stowe and confirmed their original idea that there are remarkable similarities between this disorder of Bedlington terriers and Wilson's disease.

Is it time to reconsider current guidelines for copper content in commercial dog foods?

“…Specifically, a recommendation was made to replace feed-grade copper oxide in canine diet formulations with more bioavailable forms of copper, such as copper sulfate. 10,a Mean hepatic copper concentration in dogs has progressively increased from < 10 µg/g (measured on a dry-weight basis) in 1929 to 200 µg/g in 1982 and 453 µg/g in 1995, 1,4,[11][12][13][14][15][16][17][18][19][20][21] and results of various studies suggest that high hepatic copper concentrations in dogs reflect high copper content in commercial dog foods. For example, a study 4 of Labrador Retrievers with and without chronic hepatitis found that hepatic copper concentrations were significantly higher after the recommendation to alter sources of copper in commercial dog foods than they had been before that change in formulation.…”

Genetic Modifiers of Liver Injury in Hereditary Liver Disease

“…The Beddlington terriers that develop copper overload were originally thought to have a defect related to WD, but instead were found to have a different genetic defect accounting for their copper overload. 13,14 This abnormality in copper handling that causes hepatic copper overload is a result of a defect in MURR1, also called COMMD1. The function of the gene product of MURR1 is still uncertain, but it has been postulated as controlling a step in copper excretion after ATP7B or modulates ATP7B function in some manner.…”

Sixteen years of canine hepatic copper concentrations within normal reference ranges in dogs fed a broad range of commercial diets

“…10 Previous studies have demonstrated increases in liver copper concentrations from < 10 ppm in 1929 to 200 ppm in 1982 and 453 ppm in 1995, mostly in predisposed breeds such as Bedlington Terriers, West Highland White Terriers, and Labrador Retrievers. [10][11][12][13][14][15][16][17][18][19][20][21][22] In addition to this observation, some investigators have drawn conclusions that high hepatic concentrations in dogs reflect high copper content in commercial dog food that may be greater than the biological requirement for dogs. 1 However, the exact cause for the increase in copper-associated hepatopathy incidences is unknown.…”