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Protocol for Production of a Genetic Cross of the Rodent Malaria Parasites
Published on: January 3, 2011
Identification of a novel cerebral malaria susceptibility locus (Berr5) on mouse chromosome 19
1Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Abstract:
Cerebral malaria (CM) is an acute, generally lethal condition characterized by high fever, seizures and coma. The genetic component to CM can be investigated in mouse models that vary in degree of susceptibility to infection with Plasmodium berghei ANKA. Using survival time to measure susceptibility in an informative F2 cross (n=257), we identified linkage to chromosome 19 (Berr5 (Berghei resistance locus 5), LOD=4.69) controlling, in part, the differential response between resistant BALB/c and susceptible C57BL/6 progenitors. BALB/c alleles convey increased survival through the cerebral phase of infection but have no quantitative effect on parasitemia during the later, anemic phase. The Berr5 locus colocalizes with three other immune loci, including Trl-4 (tuberculosis resistance), Tsiq2 (T-cell secretion of IL-4) and Eae19 (experimental allergic encephalitis 19), suggesting the possibility of a common genetic effect underlying these phenotypes. Potential positional candidates include the family of Ifit1-3 (interferon-inducible protein with tetratricopeptide repeats 1-3) and Fas.
Insights
Researchers identified a new genetic locus, Berr5 on chromosome 19, that influences survival in mouse models of cerebral malaria (CM). BALB/c mouse alleles at this locus improve survival during the critical cerebral phase of infection.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Cerebral malaria (CM) is a severe and often fatal complication of Plasmodium infection.
- Mouse models are crucial for investigating the genetic underpinnings of CM susceptibility.
- BALB/c and C57BL/6 mice exhibit differential susceptibility to Plasmodium berghei ANKA-induced CM.
Purpose of the Study:
- To identify genetic loci controlling differential susceptibility to cerebral malaria in a mouse model.
- To investigate the genetic basis for resistance and susceptibility to CM using an F2 cross.
Main Methods:
- An informative F2 cross (n=257) between resistant BALB/c and susceptible C57BL/6 mice was generated.
- Survival time was used as a quantitative trait to measure CM susceptibility.
- Linkage analysis was performed to identify quantitative trait loci (QTLs).
Main Results:
- A significant linkage locus, Berr5 (Berghei resistance locus 5), was identified on chromosome 19 (LOD=4.69).
- BALB/c alleles at the Berr5 locus conferred increased survival during the cerebral phase of CM.
- Berr5 did not significantly affect parasitemia during the later, anemic phase of infection.
- The Berr5 locus colocalizes with other immune-related loci, suggesting shared genetic regulation.
Conclusions:
- The Berr5 locus on chromosome 19 plays a significant role in modulating survival during the cerebral phase of malaria.
- Identifying Berr5 provides a new target for understanding the genetic control of CM.
- The colocalization of Berr5 with other immune loci suggests potential pleiotropic effects of genes in this region.
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