Trading mouse blood for human blood.

In a research effort that one admiring scientist calls a "tour de force," a California team has genetically engineered mice to have sickle-cell anemia. This debilitating, often deadly human blood disorder results from a mutation in beta-globin, a protein subunit of hemoglobin, the oxygen-carrying molecule of red blood cells. Blood cells with the mutant protein have trouble holding oxygen and develop a sickle shape.

Scientists had previously added the human genes for mutant beta-globin and for normal alpha-globin, the other hemoglobin subunit, to mice. The animals' own globins, however, prevented the resulting blood cells from sickling.

In the new effort, Chris Paszty of the Lawrence Berkeley (Calif.) National Laboratory and his colleagues created mice that had the human beta-globin and alpha-globin genes and deactivated mouse globin genes. The mice also had the human gamma-globin gene, used to make hemoglobin during fetal development. "The goal was to create a mouse that generates only human hemoglobin," says Paszty.

The researchers found that mice thrive with normal human hemoglobin. More important, mice with the sickle-cell mutation in their added human beta-globin gene experienced anemia, liver and kidney damage, and enlarged spleens. "The mice are developing the classic multiorgan pathology of sickle-cell disease," says Paszty, who adds that the mice should be useful in testing potential new therapies.