Researchers have known for some time that in order to develop normally, embryos require adequate amounts of certain key nutrients. Copper, it appears, is one such critical substance. Indeed, according to studies published today in the Proceedings of the National Academy of Sciences, a genetic mutation leading to the loss of a protein that delivers copper to cells can inhibit embryonic development completely.

"Copper is an essential micronutrient, which is required for vital biochemical reactions within cells," University of Michigan researcher Dennis Thiele, a director of one of the studies, says. "Without copper, cells can't produce energy, metabolize iron or detoxify free radicals. Without copper, we can't grow blood vessels, synthesize neuropeptides that control muscle contractions, or make the collagen that gives our skin its elasticity." But to enter the cells, the researchers report, copper needs a very specific chaperone, a protein dubbed Ctr1p. "Ctr1 escorts copper through the cell's surface membrane," Thiele explains, "and then hands it off to at least three other proteins, which deliver it to specific compartments inside the cell."

Earlier research had shown that Ctr1 transports copper in yeast cells, but its function in mammals was unknown. In order to determine whether the protein performs the same task in mammals, the researchers bred mice that had only one functional copy of the gene that makes Ctr1. The resulting animals appeared normal, but the copper levels in their brains and spleens were about half of that found in their normal counterparts. In another experiment, the investigators attempted to produce animals lacking both functional copies of Ctr1 by breeding males and females mice that were themselves missing a copy. But to their surprise, none of the 378 mice that resulted from these pairings were missing both copies of the gene. Further examination revealed that all the embryos lacking both copies had died 10 to 12 days after fertilization.

"I anticipated the importance of copper in development, but I didn't expect it to be so critical that all the mouse embryos without Ctr1 would die before birth," Thiele says. "Based on these results, it wouldn't surprise me to find that human embryos lacking both copies of Ctr1 are aborted spontaneously during pregnanc