Why1^MOLF/EiJ
QTL Variant Detail

Summary

• QTL variant: Why1^MOLF/EiJ
• Name: wild-derived hyperresponse 1; MOLF/EiJ
• MGI ID: MGI:3773873
• QTL: Why1 Location: unknown Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: MOLF/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased Toll-like receptor-mediated cytokine response compared to C57BL/6J. (J:131437)

Notes

Why1 and Why2 engage in epistatic interactions.

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

J:131437

Linkage analysis was performed on 82 C57BL/6J x (C57BL/6J x MOLF/EiJ)F1 backcross animals to identify QTLs associated with Toll-like receptor (TLR) mediated cytokine production. IL-6 production after stimulation of macrophages with lipoteichoic acid (LTA) was assessed as a measure of TLR-mediated cytokine responsiveness.

Significant linkage to cytokine response mapped to 49 cM on mouse Chromosome 6 near D6Mit328 (LOD=3.69). This locus is named Why1 (wild-derived hyperresponse 1). The MOLF/EiJ-derived allele confersincreased IL-6 production (cytokine response) after LTA stimulation. Irak2 (49.5 cM) is a potential candidate gene for Why1. Several polymorphisms exist between the Irak2 gene sequences of C57BL/6J and MOLF/EiJ. However, these polymorphisms do not appearto correlate with the phenotype.

Why2 (wild-derived hyperresponse 2) mapped to 41 cM on mouse Chromosome 9 near D9Mit155 (LOD=5.49). This locus appears to act negatively with MOLF/EiJ-derived alleles conferring decreased IL-6 production. The QTL interval spans 23 cM. Microarray analysis identified Irak1bp1 as a potential candidate gene displaying 20-fold expression difference between C57BL/6J and MOLF/EiJ. Northern blot analysis showed increased Irak1bp1 expression in MOLF/EiJ macrophages after LTA stimulation compared to C57BL/6J macrophages.

Why1 (chr6) and Why2 (chr9) exhibit significant epistatic interaction (LRS=48.1). Authors hypothesize Why2 evolved as a negative regulator of the pro-inflammatory effects of Why1.

References

• Original: J:131437 Conner JR, et al., Forward genetic analysis of Toll-like receptor responses in wild-derived mice reveals a novel antiinflammatory role for IRAK1BP1. J Exp Med. 2008 Feb 18;205(2):305-14
• All: 3 reference(s)