Identification of the Plasmodium berghei resistance locus 9 linked to survival on chromosome 9

Malaria Journal

Research

Elizabeth A Winzeler¹  Selina ER Bopp²  Clarissa Valim³  John R Walker⁴  Christian Schmedt⁴  S Whitney Barnes⁴  Evelyn Rodrigo⁴  Mary Frazer⁴  James Watson⁴  Gonzalo E González-Páez⁵ 

[1] Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA;Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, USA;Harvard School of Public Health, Boston, MA, USA;Harvard School of Public Health, Boston, MA, USA;The Genomics Institute of the Novartis Research Foundation, La Jolla, CA, USA;The Scripps Research Institute, La Jolla, CA, USA;

关键词: Plasmodium berghei;    Experimental cerebral malaria;    Quantitative trait locus;    Malaria;    Basophil;    Chromosome mapping;    Mouse;   

DOI  :  10.1186/1475-2875-12-316

 received in 2013-04-18, accepted in 2013-08-25,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundOne of the main causes of mortality from severe malaria in Plasmodium falciparum infections is cerebral malaria (CM). An important host genetic component determines the susceptibility of an individual to develop CM or to clear the infection and become semi-immune. As such, the identification of genetic loci associated with susceptibility or resistance may serve to modulate disease severity.MethodologyThe Plasmodium berghei mouse model for experimental cerebral malaria (ECM) reproduces several disease symptoms seen in human CM, and two different phenotypes, a susceptible (FVB/NJ) and a resistant mouse strain (DBA/2J), were examined.ResultsFVB/NJ mice died from infection within ten days, whereas DBA/2J mice showed a gender bias: males survived on average nineteen days and females either died early with signs of ECM or survived for up to three weeks. A comparison of brain pathology between FVB/NJ and DBA/2J showed no major differences with regard to brain haemorrhages or the number of parasites and CD3+ cells in the microvasculature. However, significant differences were found in the peripheral blood of infected mice: For example resistant DBA/2J mice had significantly higher numbers of circulating basophils than did FVB/NJ mice on day seven. Analysis of the F2 offspring from a cross of DBA/2J and FVB/NJ mice mapped the genetic locus of the underlying survival trait to chromosome 9 with a Lod score of 4.9. This locus overlaps with two previously identified resistance loci (char1 and pymr) from a blood stage malaria model.ConclusionsSurvival best distinguishes malaria infections between FVB/NJ and DBA/2J mice. The importance of char1 and pymr on chromosome 9 in malaria resistance to P. berghei was confirmed. In addition there was an association of basophil numbers with survival.

【 授权许可】

CC BY   
© Bopp et al.; licensee BioMed Central Ltd. 2013