New canine models of copper toxicosis: diagnosis, treatment, and genetics

Abstract

The One Health principle recognizes that human health, animal health, and environmental health are inextricably linked. An excellent example is the study of naturally occurring copper toxicosis in dogs to help understand human disorders of copper metabolism. Besides the Bedlington terrier, where copper toxicosis is caused by a mutation in the COMMD1 gene, more complex hereditary forms of copper-associated hepatitis were recognized recently in other dog breeds. The Labrador retriever is one such breed, where an interplay between genetic susceptibility and exposure to copper lead to clinical copper toxicosis. Purebred dog populations are ideal for gene mapping studies, and because genes involved in copper metabolism are highly conserved across species, newly identified gene mutations in the dog may help unravel the genetic complexity of different human forms of copper toxicosis. Furthermore, increasing knowledge with respect to diagnosis and treatment strategies will benefit both species.

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

“…Details and evidence for breed, sex, and age predispositions are summarized in Supporting Information Table S1. There is strong evidence in ≥2 studies for an increased prevalence of CH in BT, Doberman Pinschers, LR, Dalmatians, American and English Cocker Spaniels, English Springer Spaniels, and West Highland White Terriers in several countries. In addition, in Sweden the Scottish Terrier, and in the United Kingdom the Cairn Terrier, Great Dane, Samoyed, Yorkshire Terrier, and Jack Russell Terrier are predisposed .…”

“…The overall mean age when clinical signs are reported is 7.2 years (11 studies, n = 983 dogs). Disease duration before diagnosis is unclear . Reported age ranges in specific breeds are shown in Supporting Information Table S1.…”

“…Details and evidence for breed, sex, and age predispositions are summarized in Supporting Information Table S1. There is strong evidence in ≥2 studies for an increased prevalence of CH in BT, 24,35 Doberman Pinschers, 7,20,[43][44][45]150,[153][154][155][156]158,162,[169][170][171][172][173] LR, 8,10,14,21,27,138,158,162,163,168,169,172 Dalmatians, [39][40][41]157,158,169,174 American and English Cocker Spaniels, 27,48,156,157,162,163,165,169,175 English Springer Spaniels, 158,…”

“…Disease duration before diagnosis is unclear. 27,147,[157][158][159][160][161][162][163]169,172,175 Reported age ranges in specific breeds are shown in Supporting Information Table S1. Dalmatians, Doberman…”

Gene expression patterns in the progression of canine copper-associated chronic hepatitis

“…Familial copper toxicosis is also common in several dog breeds[19–24]. Due to the limited genetic variability within inbred dog populations[25], dogs are used as large animal model to dissect genetics basis of (complex) inherited diseases[26–29]. A deletion of exon 2 of the COMMD1 gene was found in affected Bedlington terriers[24], leading to undetectable protein in lever homogenates of affected dogs[30].…”