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Antimicrobial Agents and Chemotherapy, October 2009, p. 4533-4536, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00519-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Improved Murine Model of Malaria Using Plasmodium falciparum Competent Strains and Non-Myelodepleted NOD-scid IL2R{gamma}null Mice Engrafted with Human Erythrocytes {triangledown}

María Belén Jiménez-Díaz,1 Teresa Mulet,1 Sara Viera,1 Vanessa Gómez,1 Helen Garuti,1 Javier Ibáñez,1 Angela Alvarez-Doval,1 Leonard D. Shultz,2 Antonio Martínez,1 Domingo Gargallo-Viola,1,{dagger} and Iñigo Angulo-Barturen1*

ID CEDD Diseases of the Developing World, GlaxoSmithKline, c/Severo Ochoa 2, 28760, Tres Cantos, Spain,1 The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 046092

Received 20 April 2009/ Returned for modification 10 June 2009/ Accepted 8 July 2009

Murine models of Plasmodium falciparum malaria may become crucial tools in drug discovery. Here we show that non-myelodepleted NOD-scid IL2R{gamma}null mice engrafted with human erythrocytes support an infectious burden up to tenfold higher than that supported by engrafted NOD-scid β2microglobulinnull 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.

* Corresponding author. Mailing address: GlaxoSmithKline, ID CEDD Diseases of the Developing World, Drug Discovery Biology, Therapeutic Efficacy, c/Severo Ochoa, 2, Tres Cantos 28760 Madrid, Spain. Phone: 34 91 807 57 40. Fax: 34 91 807 05 95. E-mail: inigo.x.angulo{at}gsk.com

{triangledown} Published ahead of print on 13 July 2009.

{dagger} Present address: Department of Toxicology and Safety Pharmacology, Ferrer Grupo, Barcelona, Spain.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4533-4536, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00519-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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