PROTECTION FROM LETHAL MALARIA IN TRANSGENIC MICE EXPRESSING SICKLE HEMOGLOBIN

Previous studies from our laboratories have shown that transgenic mice expressing high levels of beta(s) globin are well-protected from Plas modium chabaudi adami and partially protected against P berghei (Shear et al, Blood81:222, 1993). We have now infected transgenic mice expre ssing low (39%), intermediate (57%), and high (75%) levels of beta(s) with the virulent strain of P yoelii (17XL) that appears to cause cere bral malaria. We find that the level of protection in these three grou ps of mice correlates positively with the level of beta(s) chain expre ssion in the mice. Seven of nine mice expressing the high level of bet a(s) recovered from infection, as did 7 of 9 mice expressing the inter mediate level of beta(s). Control mice and mice expressing the lower l evel of beta(s) all succumbed to infection. In mice expressing high an d intermediate levels of beta(s), parasites were found almost exclusiv ely in reticulocytes during recovery, suggesting that mature red blood cells expressing beta(s) are more resistant than reticulocytes. These studies confirm epidemiologic data and offer insight into the mechani sm of protection of sickle trait individuals against falciparum malari a. (C) by The American Society of Hematology.