Grass1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Grass1^DBA/2J
• Name: group A streptococcal sepsis severity 1; DBA/2J
• MGI ID: MGI:3789154
• QTL: Grass1 Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to group A streptococcal sepsis compared to C57BL/6J. (J:134374)
• Inheritance: Dominant

Notes

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

J:134374

Linkage analysis was performed on 30 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred strains to identify QTL associated with susceptibility to streptococcal sepsis. Groups of 5-26 animals at age 40-120 days were injected with a hypervirulent strain of streptococcus and phenotyped for weight loss and mortality every 8 hours for a period of 6 days. Bacteremia and bacterial dissemination to the spleen were also assessed as quantitative traits. A panel of 3795 SNPs and polymorphic microsatellite markers were used for genome scan.

Significant linkage to survival (LRS=34.2) and bacteremia 24 hours after infection (LS=24.5) mapped to mouse Chromosome 2 between 22 Mb - 34 Mb. This locus is named Grass1 (group A streptococcal sepsis severity 1). C57BL/6J-derived alleles at Grass1 conferrecessively-inherited resistance to group A streptococcal sepsis while DBA/2J-derived alleles confer dominantly-inherited susceptibility. The Grass1 QTL interval was narrowed to a region between 23.37 Mb - 33.15 Mb by analyzing recombination breakpoints within the BXD strain set. A search for candidate genes in this interval displaying differential spleen mRNA expression between DBA/2J and C57BL/6J revealed up-regulation of Il1 (73 cM), Il1rn (10 cM), Ptges (24 cM) and Ptges2 in susceptible strains. Il1a, Il1rn and Ptges are involved in lipid metabolism and innate immunity pathways.

Suggestive linkage to survival mapped distal to Grass1 on chromosome 2 at 125 Mb - 150 Mb with LRS=12. This locus also displays suggestive linkage to bacteremia (LRS=17) and bacterial dissemination to the spleen (LRS=15).

Suggestive linkage to survival after streptococcal infection mapped to mouse Chromosome X.

References

• Original: J:134374 Abdeltawab NF, et al., An unbiased systems genetics approach to mapping genetic loci modulating susceptibility to severe streptococcal sepsis. PLoS Pathog. 2008 Apr;4(4):e1000042
• All: 1 reference(s)