Transgenic mice expressing human sickle hemoglobin are partially resistant
to rodent malaria
HL Shear, EF Roth , ME Fabry, FD Costantini, A Pachnis, A Hood and RL Nagel
Department of Medical and Molecular Parasitology, New York University
Medical Center.
The polymorphic frequency of the gene for beta s-globin involved in the
generation of sickle trait and sickle cell anemia in the human population
is caused by the enhanced resistance of sickle trait individuals to
Plasmodium falciparum malaria, as supported by epidemiologic and in vitro
studies. However, the mechanism for the protective effect of sickle
hemoglobin in vivo has not been fully defined. The generation of transgenic
mice expressing high levels of human beta s- and alpha-chains has allowed
us to study this phenomenon in vivo in an experimental model. We infected
the transgenic beta s mice with two species of rodent malaria and found a
diminished and delayed increase in parasitemia as compared with controls.
This is in contrast to our previous studies involving the introduction of a
beta A transgene, which does not alter the infection. The use of this model
allowed us to address the question of the mechanism of protection against
malaria in mice expressing sickle hemoglobin. We find that splenectomy of
transgenic mice completely reverses the protection against Plasmodium
chabaudi adami infection. The results reported have shown a relationship
between the presence of the beta s gene product and partial resistance to
malaria in an experimental model in vivo and shows that the spleen plays an
important role in this protection.
Volume 81,
Issue 1,
pp. 222-226,
01/01/1993
Copyright © 1993 by The American Society of Hematology
