Il4ppq^NZB/Slc
QTL Variant Detail

Summary

• QTL variant: Il4ppq^NZB/Slc
• Name: IL-4 producing potential QTL; NZB/Slc
• MGI ID: MGI:3702121
• QTL: Il4ppq Location: Chr7:124513662-128819324 bp Genetic Position: Chr7, cM position of peak correlated region/allele: 68.16 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: NZB/NSlc

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased IL-4 producing potential in splenic T-cells compared to NZW/Slc. (J:117863)

Notes

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

J:117863

Linkage analysis was performed to identify QTL associated with IL-4 producing potential in anti-CD3 mAb-stimulated spleen cells from 142 (NZB/Slc x NZW/Slc)F1 x NZW/Slc backcross mice at 2 months of age. Parental strain NZB/Slc is susceptible to systemiclupus erythematosus (SLE) and displays limited IL-4 potential whereas parental strain NZW/Slc is SLE-resistant and displays high IL-4 potential. Genome scan was performed using 117 polymorphic genetic markers.

Significant linkage to IL-4 potential mapped to mouse Chromosome 7 between D7Mit255 (61 cM) and D7Mit103 (63.5 cM) with LOD=4.3. This locus is named Il4ppq (IL-4 producing potential QTL) and maps near the Il4ra gene at 62 cM. Animals heterozygous at Il4ppq display significantly decreased IL-4 production compared to animals homozygous for NZW/Slc-derived alleles at Il4ppq. This locus is also associated with positive proteinuria in a NZW/Slc x (NZW/Slc x BXSB)F1 backcross population. In fact, backcross animals heterozygous for NZW/Slc and BXSB alleles at Il4ppa/Il4ra display significantly increased incidence of proteinuria after 4 months of age.

Since Il4ra is an obvious candidate gene, sequence analysis revealed 17 coding region nucleotide substitutions between NZB/Slc and NZW/Slc. NZB/Slc and BXSB (another SLE-susceptible strain with limited IL-4 potential) have the same Il4ra sequence as C57BL/6J except for a single nucleotide change at position 954, and NZW/Slc has the same Il4ra sequence as BALB/c.

References

• Original: J:117863 Shiroiwa W, et al., IL-4R{alpha} polymorphism in regulation of IL-4 synthesis by T cells: implication in susceptibility to a subset of murine lupus. Int Immunol. 2007 Feb;19(2):175-83
• All: 1 reference(s)