Most m RNA levels of proteins involved in copper binding, transport, and excretion were around control values in the N-CASH and CASH group.In contrast, many of these (including ATP7A, ATP7B, ceruloplasmin, and metallothionein) were significantly reduced in the DH group.Measurements on defences against oxidative stress showed a decrease in gene-expression of superoxide dismutase 1 and catalase in both groups with high copper.
Although the gene underlying Wilson's disease (ATP7B) is deficient in Long-Evans Cinnamon rats .
Here, we describe in Doberman pinschers a copper associated chronic hepatitis (also called Doberman hepatitis), characterized by micro-nodular cirrhosis with elevated hepatic copper concentrations .
However, genes ATP7B and MURR1 have been excluded by us as possible candidates by genotyping (data not shown).
The role of copper accumulation in the onset of hepatitis is still unclear.
Therefore, we investigated a spontaneous disease model of primary copper-toxicosis in Doberman pinschers so to gain insights into the pathophysiology of copper toxicosis, namely on genes involved in copper metabolism and reactive oxygen species (ROS) defences.
We used quantitative real-time PCR to determine differentially expressed genes within a target panel, investigating different groups ranging from copper-associated subclinical hepatitis (CASH) to a clinical chronic hepatitis with high hepatic copper concentrations (Doberman hepatitis, DH).Furthermore, a non-copper associated subclinical hepatitis group (N-CASH) with normal hepatic copper concentrations was added as a control.In the DH group the expression of gene products involved in copper efflux was significantly reduced, which might explain the high hepatic copper levels in this disease.ROS defences were most likely impaired in the CASH and DH group.Overall, this study describes a new variant of primary copper toxicosis and could provide a molecular basis for equating future treatments in dog and in man. Copper induced hepatitis has been described both in humans (Wilson's disease) as well as in dogs.There are several non-human models of copper toxicosis models, such as the Long-Evans Cinnamon rats and Bedlington terriers.Tags: Adult Dating, affair dating, sex dating