will eventually result in a primary deficiency of copper and potentially death.

A secondary, or conditioned, deficiency might occur even if the mother's intake of copper from the diet is adequate. Conditioned deficiencies can arise by several means. First, copper deficiency can arise through an effect of drugs or other chemicals on the metabolism of copper. Second, a conditioned embryonic or fetal deficiency of copper might arise if the mother has an excessive low intake of copper as a consequence of an underlying disease or if disease-induced changes in maternal copper metabolism reduces the transfer of copper to the conceptus. Third, nutritional interactions can produce conditioned deficiencies. These interactions can be of several types. For example, copper-binding factors, such as phytate and possible fiber, in the mother's diet can potentially reduce the amount of copper absorbed from the diet. A copper deficiency can also occur if the diet contains a high concentration of a metal with physical-chemical properties similar to those of copper; zinc, cadmium and silver are examples of metals in this category. Finally, a conditioned copper deficiency can occur as a consequence of genetic factors. Those can either be a single gene defect (e.g., Menkes disease) or multiple genes that collectively affect one or more aspects of copper metabolism. In experimental animals, multiple gene effects are typically referred to as a strain or breed effect. Those effects are discussed in more detail below.

Copper in Prenatal Development

The importance of copper for the prenatal development of mammals was shown in sheep by Bennetts et al. (1948) in their demonstration that enzootic ataxia, a disease affecting the developing fetus, could be prevented by giving the ewe additional copper during pregnancy. This disorder is characterized by spastic paralysis, especially of the hind limbs, severe incoordination, blindness in some cases, and anemia. Typically, the brains of animals with enzootic ataxia are small and characterized by collapsed cerebral hemisphoresis, shallow convolutions, and a paucity of normal myelin (Hurley and Keen 1979). Similar neonatal ataxia and brain abnormalities have been reported in newborn copper-deficient deer, goats, swine, guinea pigs, and rats (Hurley and Keen 1979, Yoshikawa et al. 1996). Copper deficiency, as evidenced by low concentrations of copper in plasma, can be induced in most mammalian species by feeding a copper-deficient diet (copper at less than 1 mg/kg of body weight compared with control diets of 8 to 15 mg/kg) for 2 to 4 weeks.

Researchers have not agreed on the biochemical bases of the brain abnormalities associated with copper deficiency during early development.



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