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Study illuminates birth defects caused by copper deficiency

biochemical processes including cellular respiration, iron oxidation, and the formation of pigments and connective tissue, Gitlin said. The signs and symptoms of copper deficiency therefore result from the impaired function of such copper-containing enzymes.

Considerable clinical and experimental data had suggested that copper is an essential nutrient for normal development, the researchers said. Children with Menkes disease harbor a mutant version of the gene encoding so-called copper-transport ATPase (ATP7A), leading to symptoms including degeneration of parts of the brain and severe failure to thrive. Similarly, in a variety of mammals, copper deficiency during pregnancy results in loss of the embryo or offspring with severe neurologic impairment and developmental defects of the heart, skeleton, and other tissues.

By studying developing zebrafish treated with drugs that interfered with copper metabolism in the current study, the researchers found that copper deficiency led to a loss of pigment and profoundly altered notochord development. Further examination also revealed other impairments, including abnormal cartilage, vascular, and neurologic development, they reported.

Careful examination of embryos treated with different doses of copper-blocking drugs or for different lengths of time uncovered a hierarchy of copper distribution within the developing embryo. For example, a 10 min drug treatment resulted in absence of pigment but a normal notochord. Extending the treatment to 20 min resulted in loss of pigment and a clearly abnormal notochord, and by 60 min, the treatment led to still other defects.

The team then screened mutant zebrafish for defects like those caused by copper deficiency, identifying one with a "striking resemblance--particularly in its lack of melanin pigment and wavy notochord--to the chemically induced copper-deficient" animals. The zebrafish harbored a mutation in the copper transport gene ATP7A tha
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
8-Aug-2006


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