Thursday, September 27, 2012
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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)
were deleted to generate immunodeficiency, while fumarylacetoacetate
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
SciBX 5(38); doi:10.1038/scibx.2012.1015
Published online Sept. 27, 2012
Patented; available for
purchase from Yecuris
Vaughan, A.M. et al. J.
Clin. Invest.; published online Sept. 10, 2012;
Contact: Stefan H.I. Kappe, Seattle Biomedical Research
Institute, Seattle, Wash.
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