Abnormal cellular copper metabolism in the blotchy mouse.

Defective copper metabolism was demonstrated in male mice bearing the blotchy (Moblo/y) allele at the mottled locus on the X-chromosome. Copper absorption from the gut was only 64% of that found in normal mice and hepatic copper levels were only 56% of the controls. Ceruloplasmin and heart cytochrome c oxidase activities were normal, yet lysyl oxidase activity from cultured fibroblasts was only 45% of control levels. Copper accumulated in fibroblasts cultured from these mutants to values that were five times normal. The accumulation of copper in the fibroblasts was associated with a protein of approximately 12,000 molecular weight.