title: Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria.
abstract: 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.
authors.affiliation: Department of Medical and Molecular Parasitology, New York University Medical Center.
authors.forename: H L
authors.initials: HL
authors.lastname: Shear
authors.forename: E F
authors.initials: EF
authors.lastname: Roth
authors.forename: M E
authors.initials: ME
authors.lastname: Fabry
authors.forename: F D
authors.initials: FD
authors.lastname: Costantini
authors.forename: A
authors.initials: A
authors.lastname: Pachnis
authors.forename: A
authors.initials: A
authors.lastname: Hood
authors.forename: R L
authors.initials: RL
authors.lastname: Nagel
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000469:parasitology / Q000648:ultrastructure; D015870:Gene Expression; D005914:Globins / Q000235:genetics; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D008288:Malaria / Q000097:blood* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010962:Plasmodium berghei; D016788:Plasmodium chabaudi; D013156:Splenectomy
chemical_list: D006451:Hemoglobin, Sickle; D005914:Globins