Transgenic and mutant animal models to study mechanism of protection of red cell genetic defects against malaria

Abstract

Malaria, caused by members of the genusPlasmodia, is still the most prevalent parasitic disease in the world. In an attempt to understand genetic factors conferring resistance to malaria, mouse models of thalassemia, sickle trait, and ankyrin and spectrin deficiency were studied during infection with species of malaria infectious to rodents. Although growth ofP. falciparum is not inhibited in thalassemic erythrocytes in culture, mice carrying a β-thalassemia mutation were protected fromPlasmodium chabaudi adami, supporting epidemiologic findings. Transgenic mice expressing β^s hemoglobin were also significantly protected from two species of rodent malaria. Importantly, a significant role for the spleen in protection in the β^s transgenic mice was found. Finally, mice deficient in spectrin and ankyrin were studied with respect to their ability to support the growth of malaria. It was found that spectrin deficient mice were almost completely refractory toP. chabaudi adami andP. berghei. These models will allow further study of host factors in resistance to malaria.