title: Identification of the Plasmodium berghei resistance locus 9 linked to survival on chromosome 9.
abstract: BACKGROUND
  One 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  FVB/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.
  
  
  CONCLUSIONS
  Survival 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.
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA, USA. sbopp@hsph.harvard.edu.
authors.forename: Selina E R
authors.initials: SE
authors.lastname: Bopp
authors.forename: Evelyn
authors.initials: E
authors.lastname: Rodrigo
authors.forename: Gonzalo E
authors.initials: GE
authors.lastname: González-Páez
authors.forename: Mary
authors.initials: M
authors.lastname: Frazer
authors.forename: S Whitney
authors.initials: SW
authors.lastname: Barnes
authors.forename: Clarissa
authors.initials: C
authors.lastname: Valim
authors.forename: James
authors.initials: J
authors.lastname: Watson
authors.forename: John R
authors.initials: JR
authors.lastname: Walker
authors.forename: Christian
authors.initials: C
authors.lastname: Schmedt
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Winzeler
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology; D002899:Chromosomes, Human, Pair 9; D004195:Disease Models, Animal; D060467:Disease Resistance; D005260:Female; D056426:Genetic Loci; D006801:Humans; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology*; D016019:Survival Analysis
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