Gene-expression profiling discriminates between cerebral malaria (CM)-susceptible mice and CM-resistant mice

Nicolas F Delahaye1, Nicolas Coltel, Denis Puthier

  • 1Laboratoire de Pharmacogenetique des Maladies Parasitaires-EA864, Universite de la Mediterranee-IFR48, Marseille, France.

Insights

Genetic control influences cerebral malaria (CM) development in mice. Gene expression analysis identified key genes linked to CM resistance and susceptibility, offering insights for human disease severity studies.

Area of Science:

  • Genetics
  • Immunology
  • Neuroscience

Background:

  • Cerebral malaria (CM) development in mice infected with Plasmodium berghei ANKA is genetically determined.
  • Understanding the genetic basis of CM susceptibility is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate brain gene-expression patterns in genetically CM-resistant and CM-susceptible mouse strains.
  • To identify candidate genes associated with resistance or susceptibility to mouse CM.

Main Methods:

  • Utilized cDNA microarrays for transcriptional profiling in defined mouse strains (BALB/c, DBA/2, C57BL/6, CBA/J).
  • Applied rigorous statistical methods, including cluster analysis and Welch t test with a 5% false discovery rate.
  • Combined transcriptional profiling with gene ontology analysis.

Main Results:

  • Identified 69 genes that perfectly discriminated between mouse strains and CM resistance/susceptibility.
  • Discovered 31 genes with consistently differential expression between CM-resistant and CM-susceptible mice.
  • Gene ontology analysis indicated immune response-related genes are linked to CM susceptibility.

Conclusions:

  • Microarray analysis is a valuable tool for identifying candidate genes in mouse CM.
  • Candidate genes identified in mice warrant further investigation for association with human CM severity.