Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  6
• Reference
  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
• ID
  MGI:3773870

Genes

Gene	Assay Type
Why1	visible phenotype
D6Mit328	PCR
Irak2	reported elsewhere

Notes

• Experiment
  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.