Char4^A/J
QTL Variant Detail

Summary

• QTL variant: Char4^A/J
• Name: P. chabaudi malaria resistance QTL 4; A/J
• MGI ID: MGI:2155273
• QTL: Char4 Location: Chr3:69625509-100655290 bp Genetic Position: Chr3, cM position of peak correlated region/allele: 56.54 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers malaria susceptibility compared to C57BL/6J.
• Inheritance: Dominant

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:71471

199 animals from a (AcB55/Mcg x A/J)F2 intercross were used to map QTLs associated with malaria resistance. AcB55/Mcg is a highly resistant recombinant congenic strain derived from progenitor strains A/J (susceptible) and C57BL/6J (resistant). AcB55/Mcg is homozygous for malaria susceptibility alleles at Char1 (on mouse Chromosome 9) and Char2 (on mouse Chromosome 8) to maximize identification of novel malaria resistance loci in the current screen. Male and female animals 8-12 weeks of age were infected with Plasmodium chabaudi and assessed for parasitemia. Significant linkage was detected on mouse Chromosome 3 near D3Mit109 (LOD = 6.57 at approximately 61.8 cM) and the locus was named Char4 (P. chabaudi malaria resistance QTL 4). Resistance to malaria appears to be recessively inherited at Char4 and there is evidence of additive interactions with a codominantly or dominantly inherited locus on mouse Chromosome 10 (LOD = 2.53 near D10Mit189).

J:86735

Recombinant congenic strain AcB55 is resistant to malaria and is derived from parental strains A/J (susceptible) and C57BL/6J (resistant). An F2 cross between AcB55 and A/J was analyzed for linkage to malaria resistance. A locus on mouse Chromosome 3 was detected in linkage to malaria resistance and reticulocytosis and mapped to Char4 between D3Mit22 (33.7 cM) and D3Mit75 (49 cM). Peak linkage to reticulocytosis occurs at D3Mit175 (41 cM). A/J-derived alleles confer recessively-inherited reticulocytosis at this locus.

Pklr is a strong candidate gene mapping near Char4. Sequence analysis of Pklr revealed a loss of function mutation caused by an isoleucine to asparagines substitution at residue 90 (T269A) in the AcB55 strain. This mutation segregated with reduced peak parasitemia and reduced mortality after infection with Plasmodium chabaudi.

References

• Original: J:71471 Fortin A, et al., Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10793-8
• All: 2 reference(s)