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Background  Hepatic copper accumulation causes chronic hepatitis in dogs. Mutations in the copper transporters ATP7A and ATP7B were, respectively, associated with attenuation and enhancement of hepatic copper concentrations in Labrador Retrievers. There is a predisposition of Dobermanns to hepatitis with increased hepatic copper concentrations.    Objectives  To investigate whether the  ATP7A :c.980C>T and  ATP7B :c.4358G>A mutations identified in Labrador Retrievers were associated with hepatic copper concentrations in Dobermanns.    Animals  Dobermanns from the Netherlands (n = 122) and the United States (n = 78).    Methods  In this retrospective study, mutations in  ATP7A  and  ATP7B  were investigated as risk factors for hepatic copper accumulation in Dobermanns. Liver biopsies of 200 Dobermanns were evaluated by histochemical copper staining, quantitative copper measurement, or both modalities.  ATP7A  and  ATP7B  genotypes were obtained by Kompetitive Allele Specific PCR. A linear regression model was used to investigate an association between genotype and hepatic copper concentrations.    Results  The  ATP7A :c.980C> T  was identified in both Dutch (2 heterozygous individuals) and American Dobermanns. In the American cohort, the minor allele frequency of the mutation was low (.081) and a possible effect on hepatic copper concentrations could not be established from this data set. A significant association of the  ATP7B :c.4358G>A variant with increased hepatic copper concentrations in Dobermanns was observed.    Conclusions and Clinical Importance  The  ATP7B :c.4358G>A variant could be a contributor to hepatic copper accumulation underlying the risk of development of copper‐associated hepatitis in breeds other than the Labrador Retriever.

Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs