Improved murine model of malaria using Plasmodium falciparum competent strains and non-myelodepleted NOD-scid IL2Rgammanull mice engrafted with human erythrocytes.
Murine models of Plasmodium falciparum malaria may become crucial tools in drug discovery. Here we show that non-myelodepleted NOD-scid IL2Rgamma(null) mice engrafted with human erythrocytes support an infectious burden up to tenfold higher than that supported by engrafted NOD-scid beta2microglobulin(null) mice. The new model was validated for drug discovery and was used to assess the therapeutic efficacy of 4-pyridones, selective inhibitors of P. falciparum cytochrome bc1.
Jiménez-Díaz
María Belén
MB
ID CEDD Diseases of the Developing World, GlaxoSmithKline, c/Severo Ochoa 2, 28760, Tres Cantos, Spain.
Mulet
Teresa
T
Viera
Sara
S
Gómez
Vanessa
V
Garuti
Helen
H
Ibáñez
Javier
J
Alvarez-Doval
Angela
A
Shultz
Leonard D
LD
Martínez
Antonio
A
Gargallo-Viola
Domingo
D
Angulo-Barturen
Iñigo
I
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D002738:Chloroquine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011728:Pyridones / Q000627:therapeutic use; D011739:Pyrimethamine / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D053631:Interleukin Receptor Common gamma Subunit; D011728:Pyridones; C534143:4-pyridone; D000077332:Artesunate; D002738:Chloroquine; D011739:Pyrimethamine