Hfgi1^BALB/cOla
QTL Variant Detail

Summary

• QTL variant: Hfgi1^BALB/cOla
• Name: Helicobacter felis gastric inflammation 1; BALB/cOla
• MGI ID: MGI:3722332
• QTL: Hfgi1 Location: unknown Genetic Position: Chr9, Syntenic

Variant origin

• Strain of Specimen: BALB/cOla

Variant description

• Allele Type: QTL

Notes

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

J:123483

Linkage analysis was performed on 385 mice from a (C57BL/6/Ola x BALB/cOla)F2 intercross to identify QTLs associated with lymphocyte response to Helicobacter felis infection. Parental strain C57BL/6Ola displays severe gastric inflammation and significantly elevated splenic lymphocyte proliferation after 12 weeks of infection with H. felis compared to parental strain BALB/cOla. Genome scan was performed using 90 SNP markers at an average spacing of 20 cM. Significant linkage to H. felis-induced gastric inflammation mapped to mouse Chromosome 9. This locus was subsequently fine-mapped to two separate loci. The proximate locus, named Hfgi1 (Helicobacter felis gastric inflammation 1), maps between 24.4 cM - 44.7 cM with LOD=5.0 and explains 6.8% of the phenotypic variance. The distal locus, named Hfgi2 (Helicobacter felis gastric inflammation 2), maps to 44.7 cM - 53.8 cM with LOD=8.33 and explains 9.5% of the variance. C57BL/6J-derived alleles at Hfgi1 and Hfgi2 confer increased lymphoproliferative responsein infected F2 animals.

Thirty-eight candidate genes were identified in the Hfgi1 and Hfgi2 QTL intervals based on gene function. RT-PCR was performed on stomach and spleen RNA from infected and uninfected C57BL/6Ola and BALB/cOla animals to identify candidate genes exhibiting differential expression. Tlr9 (106 Mb) maps to the Hfgi2 interval and was of particular interest. Tlr9 displays decreased expression in infected C57BL/6Ola animals compared to uninfected C57BL/6Ola animals. However, the level of Tlr9 expression in C57BL/6Ola is significantly increased in both infected and uninfected animals compared to BALB/cOla. Several sequence changes are also present in the Tlr9 promoter and coding region in C57BL/6Ola and BALB/cOla. In addition, in vitro studies show the C57BL/6Ola Tlr9 promoter is more transcriptionally active than the BALB/cOla Tlr9 promoter. C57BL/6 animals homozygous for Tlr9 knockout mutation also display reduced lymphoproliferation in response to H. felis antigen challenge.

Suggestive linkage to H. felis-induced gastric inflammation mapped to 30 cM on mouse Chromosome 1 (LOD=2.36) and to 49 cM on mouse Chromosome 2 (LOD=2.07).

References

• Original: J:123483 Anderson AE, et al., TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan. Eur J Immunol. 2007 Jun;37(6):1548-61
• All: 1 reference(s)