Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis.

The accumulation of excessive amounts of copper in the livers of toxic milk mice results in gross morphologic, histologic, and ultrastructural changes that are progressive with age even though the concentrations of copper tend to decrease in mice older than 6 months. Striking differences in morphologic integrity between regenerative nodules and the intervening parenchyma were observed. Profound changes in mitochondria, endoplasmic reticulum, and nuclei as well as accumulation of microvesicular lipid droplets were observed in injured hepatocytes. By contrast, the hepatocytes of regenerative nodules appeared well preserved. Comparisons with other inherited mammalian disorders associated with hepatic copper toxicosis indicate that copper causes species specific organelle injury.