Genetic defects in copper metabolism

J Nutr. 2003 May;133(5 Suppl 1):1527S-31S. doi: 10.1093/jn/133.5.1527S.


Genetic defects in copper metabolism highlight the delicate balance mammalian systems have developed to maintain normal copper homeostasis. Menkes disease, the mottled mouse, the Atox-1-deficient mouse and the ctr1 knockout mouse reveal the importance of adequate copper intake during embryogenesis and early development, especially in the central nervous system. The toxicity associated with excess copper as manifest in Wilson disease, the toxic milk mouse, the LEC rat and copper toxicosis in the Bedlington terrier demonstrate the profound cellular susceptibility to copper overload, in particular, in the brain and liver. Ceruloplasmin (Cp) contains 95% of the copper found in human serum, and inherited loss of this protein results in diabetes, retinal degeneration and neurodegeneration. Despite normal copper metabolism, aceruloplasminemic patients and the Cp knockout mouse have disturbed iron homeostasis and mild hepatic copper retention. These genetic disorders of copper metabolism provide valuable insight into the mechanisms regulating copper homeostasis and models to further dissect the role of this essential metal in health and disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Biological Transport
  • Central Nervous System / embryology
  • Central Nervous System / growth & development
  • Copper / deficiency*
  • Copper / metabolism*
  • Deficiency Diseases / genetics*
  • Dopamine beta-Hydroxylase / genetics
  • Embryonic and Fetal Development
  • Humans
  • Liver / metabolism*
  • Superoxide Dismutase / genetics


  • Copper
  • Dopamine beta-Hydroxylase
  • Superoxide Dismutase