KNOCKOUT-TRANSGENIC MOUSE MODEL OF SICKLE-CELL DISEASE

When transgenic mice that expressed human sickle hemoglobin were mated with mice having knockout mutations of the mouse alpha-and beta-globi n genes, animals were produced that synthesized only human hemoglobin in adult red blood cells. Similar to many human patients with sickle c ell disease, the mice developed a severe hemolytic anemia and extensiv e organ pathology. Numerous sickled erythrocytes were observed in peri pheral blood. Although chronically anemic, most animals survived for 2 to 9 months and were fertile. Drug and genetic therapies can now be t ested in this mouse model of sickle cell disease.