Protection From Lethal Malaria in Transgenic Mice Expressing Sickle Hemoglobin

• Published in: Blood 1996-02, Vol.87 (4), p.1600-1603
• Main Authors: Hood, Andrew T., Fabry, Mary E., Costantini, Frank, Nagel, Ronald L., Shear, Hannah L.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Cell Count; Experimental protozoal diseases and models; Female; Hemoglobin, Sickle; Infectious diseases; Malaria - blood; Malaria - complications; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Parasitic diseases; Plasmodium yoelii; Protozoal diseases; Reticulocytes; Sickle Cell Trait - complications; Survival Analysis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.4.1600.bloodjournal8741600

Previous studies from our laboratories have shown that transgenic mice expressing high levels of βS globin are well-protected from Plasmodium chabaudi adami and partially protected against Pberghei(Shear et al, Blood81:222,1993). We have now infected transgenic mice expressing low (39%), intermediate (57%), and high (75%) levels of βs with the virulent strain of P yoelii (17XL) that appears to cause cerebral malaria. We find that the level of protection in these three groups of mice correlates positively with the level of βs chain expression in the mice. Seven of nine mice expressing the high level of βs recovered from infection, as did 7 of 9 mice expressing the intermediate level of βs. Control mice and mice expressing the lower level of βs all succumbed to infection. In mice expressing high and intermediate levels of βs, parasites were found almost exclusively in reticulocytes during recovery, suggesting that mature red blood cells expressing βs are more resistant than reticulocytes. These studies confirm epidemiologic data and offer insight into the mechanism of protection of sickle trait individuals against falciparum malaria.