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Disease models

Humanized mouse model for liver-stage malaria infection

Mice with humanized livers could be useful for identifying compounds that target the liver stage of human malarial strain Plasmodium falciparum. In the mice, recombination activating gene 2 (Rag2) and IL-2 receptor g-chain (Cd132) were deleted to generate immunodeficiency, while fumarylacetoacetate hydrolase (Fah) was deleted to kill liver cells. The mice were then repopulated with human hepatocytes. Following injection of P. falciparum sporozoites, the triple-knockout mice developed liver-stage infection. When the triple-knockout mice were crossed with nonobese diabetic (NOD) mice, the resulting mice supported transplantation of human red blood cells and allowed study of liver-stage to blood-stage infection dynamics. Next steps include using the mice to test compounds targeting liver-stage parasites (see Humanizing malaria mice,
page 6).

SciBX 5(38); doi:10.1038/scibx.2012.1015
Published online Sept. 27, 2012

Patented; available for purchase from Yecuris Corp.

Vaughan, A.M. et al. J. Clin. Invest.; published online Sept. 10, 2012;
Contact: Stefan H.I. Kappe, Seattle Biomedical Research Institute, Seattle, Wash.