Scientists using striped tropical fish to study the importance of diet in early embryo development have discovered a key to a rare, often fatal birth defect. 

"By the time most women know they are pregnant, the development of the fetus' organs is essentially complete," said Bryce Mendelsohn, a co-author of the study at Washington University School of Medicine.

"Since we currently do not understand the interaction between genetics and nutrition, the goal of this research was to understand how the lack of a specific nutrient, in this case copper, interacts with an embryo's genetics during early development."

Copper is a trace metal found in lobster, peanuts, and chocolate. Humans need copper to keep iron levels stable, form connective tissue, produce hormones and pigmentation and enable nerve functions in the brain.

Menkes disease is an inherited disorder in which humans cannot properly metabolize copper. The disease affects about one in 300,000 people, is untreatable and fatal. Children with Menkes disease have seizures, degeneration in their neurons, abnormal bone development and kinky, colourless hair. Most die before age 10.

Researchers turned to the zebrafish, a small, colourless fish that reproduces rapidly, to study the relationship between genes and nutrition during development.

The fish are a handy model since they lay eggs that are transparent and develop outside the mother's body, which allows scientists to regulate nutrients precisely during development.  

Nutritional needs

While it is known that copper supplements can help milder versions of the disease in humans, the zebrafish findings show why.

After Mendelsohn and his colleagues inserted normal cells into mutated zebrafish embryos, they found the problem isn't a lack of copper, but how well a gene called ATP7A works and how it affects the use of nutrients during early development.

Zebrafish exposed to lower doses of copper-blocking drugs showed loss of pigment. At higher doses, the fish lacked a spine-like notochord. 

The animal model may offer a way to screen compounds to see if they can restore copper-handling and treat the disorder in human embryos. 

"While it will require an enormous amount of science, this is the first time it is even within our grasp to know how an individual woman's genes might affect her nutritional requirements and the risk that her children might develop a congenital disorder," said pediatrician Jonathan Gitlin of Washington University School of Medicine in St. Louis, a co-author of the study published in Tuesday's issue of the journal Cell Metabolism.

The researchers plan to use the same approach to look at the possible role of dietary or genetic factors in other birth defects such as scoliosis or curvature of the spine.