SHORT COMMUNICATION: Functional consequences of RNA interference targeting COMMD1 in a canine hepatic cell line in relation to copper toxicosis

Abstract

SummaryA deletion in the copper metabolism (Murr1) domain containing 1 (COMMD1) gene is associated with hepatic copper toxicosis in dogs, yet evidence of copper retention in COMMD1‐depleted hepatic cells has not been shown. In a dog hepatic cell line, we analysed the copper metabolic functions after an 80% (mRNA and protein) COMMD1 reduction with COMMD1‐targeting siRNAs. Exposure to 64Cu resulted in a significant increase in copper retention in COMMD1‐depleted cells. COMMD1‐depleted cells were almost three times more sensitive to high extracellular copper concentrations. Copper‐mediated regulation of metallothionein gene expression was enhanced in COMMD1‐depleted cells. Based on the increased copper accumulation and enhanced cellular copper responses upon COMMD1 reduction, we conclude that COMMD1 has a major regulatory function for intracellular copper levels in hepatic cells.