Scientists create sickle-celled mouse.

Scientists create sickle-celled mouse

Sickle cell anemia has long been a thorn in the geneticist's side. The inhereted disease was among the first to have its underlying molecular basis revealved, yet after 30 years of intensive efforts, researchers have failed to provide a therapeutic breakthrough for th ose who suffer its complications (SN: 12/2/89, p.360).

A laboratory animal with sickle cell disease could offer new insights into the mechanisms of red-blood-cell sickling and serve as an ideal subject for experimental drugs. Indeed, scientists lay much of the blame for the slow research progress on the lack of such an animal model.

Last week, in a major step toward rectifying that situation, researchers announced they had created the world's first mice with cells that sickle. David R. Greaves of the National Institute for Medical Research in London, England, and his colleagues accomplished the feat by inserting a human sickle cell gene into embryonic mice.

Unfortunately for the scientists, the mice show no signs of the classic anemia, nor do they show a predisposition to infection or strokes -- both common among humans with the disorder. Nonetheless, the animals' red blood cells apparently do reform under low-oxygen conditions. In order ways, too, they resembler red cells in humans with sickle cell trait, a milder form of sickle cell disease.

The researchers suggest in the Jan. 11 NATURE that the animals, imperfect as they are, may prove valuable for screening anti-sickling drugs. They hope to produce sicklier versions either by breeding these mice with others suffering from a related hemoglobin abnormality called thalassemia or by boosting the expression of the inserted sickling gene.

"It may turn out, of course, that the size of the red cells, the circulation dynamics and the regulation of the microcirculation are so different in mice and men" that a mouse model may not prove particularly useful for studying the human disease, writes D.J. Weatherall of the University of Oxford, England, in a commentary accompanying the research report.