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Why1MOLF/EiJ
QTL Variant Detail
Nomenclature
QTL variant: Why1MOLF/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)
Phenotypes
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View phenotypes and curated references for all genotypes (concatenated display).
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)

Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
06/28/2022
MGI 6.20
The Jackson Laboratory