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Updated: May 12, 2026
Protocol for Production of a Genetic Cross of the Rodent Malaria Parasites
Published on: January 3, 2011
Susceptibility to lethal cerebral malaria is regulated by epistatic interaction between chromosome 4 (Berr6) and
S Torre1, R van Bruggen, J M Kennedy
1Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Abstract:
In humans, cerebral malaria is a rare but often lethal complication of infection with Plasmodium parasites, the occurrence of which is influenced by complex genetic factors of the host. We used a mouse model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA to study genetic factors regulating appearance of neurological symptoms and associated lethality. In a genome-wide screen of N-ethyl-N-nitrosourea-mutagenized mice derived from C57BL/6J (B6) and 129S1/SvImJ (129) mouse strains, we detected a strong interaction between the genetic backgrounds of these strains, which modulates ECM resistance. We have mapped a major gene locus to central chromosome 4 (log of the odds (LOD) 6.7; 79.6-97.3 Mb), which we designate Berr8. [corrected]. B6 alleles at Berr6 are associated with resistance, and are inherited in a co-dominant fashion. In mice heterozygous for Berr6 B6/129 alleles, resistance to ECM is strongly modulated by a second locus, Berr7, that maps to the proximal portion of chromosome 1 (LOD 4.03; 41.4 Mb). 129 alleles at Berr7 are associated with ECM resistance in a dosage-dependent fashion. Results are discussed in view of the possible role of this two-locus system in susceptibility to unrelated inflammatory conditions in mice and humans.
Insights
Genetic factors influence cerebral malaria severity. This study identified two key gene loci, Berr6 and Berr7, in mice that significantly modulate resistance to experimental cerebral malaria (ECM), offering insights into host susceptibility.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium infection, with host genetic factors playing a crucial role in its development.
- Understanding these genetic influences is vital for developing targeted therapies and preventative strategies.
Purpose of the Study:
- To identify and characterize host genetic factors that regulate susceptibility and resistance to experimental cerebral malaria (ECM) using a mouse model.
- To investigate the interaction between different genetic backgrounds in modulating ECM outcomes.
Main Methods:
- Genome-wide screening of N-ethyl-N-nitrosourea-mutagenized mice from C57BL/6J and 129S1/SvImJ strains infected with Plasmodium berghei ANKA.
- Quantitative trait locus (QTL) mapping to identify major gene loci associated with ECM resistance and lethality.
Main Results:
- A major gene locus, designated Berr6, was mapped to central chromosome 4, with C57BL/6J alleles conferring resistance in a co-dominant manner.
- A second locus, Berr7, on proximal chromosome 1, was identified as modulating ECM resistance in a dosage-dependent manner in heterozygous mice, with 129S1/SvImJ alleles conferring resistance.
Conclusions:
- A two-locus genetic system (Berr6 and Berr7) significantly influences resistance to experimental cerebral malaria.
- These findings provide a foundation for further research into the genetic basis of malaria pathogenesis and potential implications for other inflammatory conditions.
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