Hepatic lysosomal copper protein in dogs with an inherited copper toxicosis.

Hepatic copper overload inherited as an autosomal recessive trait in Bedlington Terriers is characterized by the presence of hepatocellular lysosomal granules of unusually high specific gravity and electron density which contain at least two thirds of the total hepatic copper. Fractionation of homogenates of liver from such affected Bedlington Terriers yielded a low-speed pellet which contained the lysosomal granules. This fraction was used for isolation of a copper-binding protein by alkaline-reduction, solubilization, fractional acetone precipitation, and gel filtration. The purified protein yielded a single band on polyacrylamide gel electrophoresis and resembled other metallothioneins in containing 15 cysteine residues and 7 to 8 atoms of copper (but no zinc) per 54 amino acid residues. No methionine, histidine, or any aromatic amino acid was present. The accumulation of this lysosomal copper protein appears to be related to the primary genetic defect which underlies the hepatic copper toxicosis of the Bedlington Terrier.