A Greek god explains anemic mice.

Scientists seeking to understand anemia caused by iron deficiency have netted a gene involved in transporting the metal into the bloodstream. The protein that the gene encodes is named hephaestin, after the Greek god Hephaestus, who wove an iron net to capture Ares and Aphrodite.

Two lines of inquiry converged on the gene, whose discovery may also help explain observations dating back to the 1920s that a lack of copper leads to iron deficiency in the body. One line was the search for the mutation that gives a strain of mice an unusual form of anemia. The animals can't use the iron available in their food to make the blood's hemoglobin molecules.

"If you give them oral iron, they don't get better. But if you give them iron intravenously or through other means that bypass the gut, they do fine," says Christopher D. Vulpe of the University of California, Berkeley.

Studies of the mice have revealed iron sitting uselessly in cells lining the intestine. Those observations suggested that the mice had no problem extracting iron from their diet but couldn't transfer the metal from intestinal cells into their circulatory systems.

As they studied the mice, Vulpe and his colleagues were also looking for relatives of the gene for ceruloplasmin, a copper-containing enzyme that participates in iron transport in organs other than the intestines, such as the liver. When they identified such a gene, they discovered that it was the same one found to be mutated in their anemic mice, the scientists report in the February NATURE GENETICS.

The investigators found that the hephaestin gene is active only in gut tissue, the right location to explain the animals' defect in iron transport from the intestines.

Since hephaestin is a relative of ceruloplasmin, it also likely employs copper. This may explain how copper deficiency can lead to anemia. The interplay between copper and iron in human metabolism has never been understood, says Vulpe. "This protein provides a connection. It needs copper to function. So, without copper, iron can't get out of the gut," he says.

Ceruloplasmin and hephaestin may facilitate iron transport by altering chemical properties of the metal, although that remains unproved. In the past few years, scientists have found several other genes involved in iron transport. When mutated, some prevent iron's absorption by the gut (SN: 8/2/97, p. 68). Others cause hemochromatosis, a surprisingly common condition in which too much iron enters the blood (SN: 1/18/97, p. 46). The role of the gene mutated in hemochromatosis is still unknown. Vulpe speculates that it increases hephaestin activity, leading to extra iron transport into blood.