A humble aquarium fish may be the key to new therapies for birth defects

anges that take place in their embryos from the moment of fertilization. The small fish have another advantage for studying the role of nutrition: Scientists can precisely regulate the nutrients that the embryo receives largely free from maternal influence.

In the paper, the researchers describe the discovery of a mutation in the zebrafish that disrupts the distribution of the critical nutrient copper within the fish cells and causes defects that are remarkably similar to those observed in children suffering from Menkes kinky hair disease, which, in its most severe form, causes degeneration and death within two to three years after birth.

"We found this mutation about two and a half years ago," said Solnica-Krezel. "Because it impairs so many aspects of normal development and causes the embryo to fall apart in two days, we named it 'Calamity.'" Six months later, she heard a talk that Gitlin gave at a scientific meeting about the results of exposing zebrafish embryos to a chemical agent that disrupts copper metabolism. She was struck by the similarity between his results and those produced by Calamity, so she approached him and they decided to collaborate.

"Lila and the other zebrafish geneticists have created all these wonderful tools," said Gitlin. "I feel like a cook that walks into this wonderfully equipped kitchen and realizes there all these wonderful recipes that he can prepare!"

The researchers explored the effect on embryo development of varying the amount of copper available and disabling different pieces of the molecular mechanisms that cells use to handle this potentially toxic material. The consequences were quite dramatic because copper-containing enzymes play a number of critical roles in the life of the cell. They are involved in the process by which a cell burns sugars and disposes of the carbon dioxide and water byproducts. They are required to produce pigmentation and develop connective tissue. These "cuproen

Contact: David F. Salisbury
Vanderbilt University

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