Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity

Rochford R.; Ohrt C.; Baresel P.C.Campo B.Sampath A.Magill A.J.Tekwani B.L.Walker L.A.

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Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity

机译：Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity

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Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/ antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第43期|17486-17491|共6页
作者
Rochford R.; Ohrt C.; Baresel P.C.Campo B.Sampath A.Magill A.J.Tekwani B.L.Walker L.A.;
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作者单位

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States;

National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, United States;

Department of Microbiology and Immunology, Upstate Medical University, Syracuse, NY 13210, United StatesMedicines for Malaria Venture, 1215 Geneva, Switzerland;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Humanized mouse model; G6PD; hemolytic;

Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity

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