Copper toxicosis in the Bedlington terrier: a diagnostic dilemma

Abstract

Diagnosis of copper toxicosis (CT) in Bedlington terriers by the quantitative and qualitative assessment of copper (Cu) in, and pathology of, biopsies has been largely superseded by a DNA-based assay which uses a microsatellite marker (C04107) linked to the CT disease allele. A retrospective study was conducted comprising 154 liver biopsies from Bedlington terriers with 22 matched DNA markers to compare the two methods in the diagnosis of CT. For the biopsy method, three categories (phenotypes) were identified based on analytical and morphological criteria: 'unaffected' in 83 samples (54 per cent), where Cu was much less than 400 microg/g, and there was an absence of visual Cu or liver damage; 'intermediate' in 18 samples (12 per cent), where Cu was less than 400 microg/g, and there was limited histochemical Cu and no/equivocal damage; and 'affected' in 53 samples (34 per cent), where Cu was greater than 400 microg/g, there was histochemical Cu and liver damage was poorly related to Cu content. In the DNA assay, which was used alone on unrelated individuals, the microsatellite marker failed to identify the CT status of any of the groups. Liver biopsy remains a reliable indicator of Cu accumulation and progressive liver disease in individual dogs. The microsatellite marker C04107 has a predictive value only when supported by a pedigree.

Two-Dimensional Mapping of Copper and Zinc in Liver Sections by Laser Ablation–Inductively Coupled Plasma Mass Spectrometry

“…Redox-active and essential trace elements such as copper show an effect of this metabolic zonation when the liver contains high amounts of copper. It has been shown, for example, that rats accumulate copper in the center of the lobules, whereas dogs show an accumulation on the fringe of the lobules, the so-called zone 1 (16 ) . Fig.…”

“…These sheep live on the shores of the small Scottish island of North Ronaldsay. Although their main diet includes different types of seaweed (15 ) containing relatively high amounts of copper, this copper is not bioavailable; hence, they have a low copper concentrations in the liver (NR liver) (16 ). The second was a commercially available lamb liver from New Zealand (NZ liver), which was used as an …”

Increased Activity of Hypoxia-Inducible Factor 1 Is Associated with Early Embryonic Lethality in Commd1 Null Mice

“…The possibility of copper overload in Commd1 Ϫ/Ϫ embryos or in the primitive placenta was analyzed using rhodamine staining of embryonic sections. This specific histochemical copper staining was used to identify copper overload in the livers of Bedlington terriers affected with copper toxicosis (18), but it did not show granular copper in 9.5-dpc Commd1 Ϫ/Ϫ embryos or in the primitive placenta (data not shown). These data imply that Commd1 Ϫ/Ϫ embryos do not have detectably elevated copper levels.…”

Not too little, not too much, but just right

“…Whereas genetic analysis of the toxic Milk Mouse33 and the Long-Evans Cinnamon rat34 shows comparable molecular defects to those found in Wilson disease, results have been less fruitful in Bedlingtons, which still present a diagnostic dilemma to breeders, owners, and veterinarians. 35 Wilson was awarded a gold medal at his doctoral dissertation for his studies of the disease that soon became associated with his name, and he was appointed as physician and pathologist to the attending staff of the National Hospital the following year at the age of 33, which position he held for 25 years until his untimely death from cancer at the peak of his reputation. He was one of the luminaries of British neurology between the wars and the epitome of a Queen Square physician, quick witted, eloquent, lucid, ironically humorous, and a master of the melodrama required in those days to demonstrate neurologic problems.…”