Prtia2^Ibut:AIRL
QTL Variant Detail

Summary

• QTL variant: Prtia2^Ibut:AIRL
• Name: pristane induced arthritis 2; Ibut:AIRL
• MGI ID: MGI:5807261
• QTL: Prtia2 Location: unknown Genetic Position: Chr5, Syntenic

Variant origin

• Strain of Specimen: Ibut:AIRL

Variant description

• Allele Type: QTL

Notes

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

J:212962

Ibut:AIRH (AIRmax, maximal inflammation) and Ibut:AIRL (AIRmin, minimal inflammation) mice are outbred stock derived from intercrossing eight inbred mouse strains, A, DBA/2, P, SWR, CBA, SJL, BALB/c and C57BL/6. Previous studies have shown that AIRmax mice were extremely susceptible to pristane-induced arthritis (PIA), whereas AIRmin mice were resistant.

The goal of this study was to identify QTL regulating PIA and to examine the interactions of the QTL with Slc11a1 alleles in modulating PIA. Slc11a1 homozygous mice for the susceptibility ^S or resistant ^R alleles with either the AIRmax or AIRmin genetic background were produced through genotype assisted matings. The resulting sublines were designated AIRmax^RR, AIRmax^SS, AIRmin^RR and AIRmin^SS. AIRmax mice homozygous for the non functional Slclla1 ^S (gly169asp) allele were more susceptible than mice homozygous for the Slc11a1 resistant ^R allele.

QTL analysis affecting the arthritis severity phenotype PIA was carried out through genome wide linkage analysis between genotypes and phenotypes by interval mapping using GridQTL version 3.1.0. Total RNA from footpads of mice on days ) and 160 after the second pristane injections were isolated using RNAspin mini kit (GE Healthcare, Buckinghamshire, UK). Mircoarray results were validated by quantitative real-time PCR using gene-specific primers.

Genome-wide scanning was performed on 290 F2 intercross mice with the PIA severity scores phenotype. Two new PIA QTL were mapped on Chromosomes 5 and 8 respectively.

Prtia2, pristane induced arthritis 2, mapped to Chr 5 with a LOD score of 4.177 in a confidence interval spanning from 95.0 to 125.0 Mb.

Prtia3, pristane induced arthritis 3, mapped to Chr 8 with a LOD score of 3.865 in a confidence interval spanning from 40.0 to 85.0 Mb.

Three suggestive QTL with LOD scores around 3.0 mapped to Chrs 7, 17 amd 19.

Among the differentially expressed genes observed in the present work, inflammatory and chemokine genes on chromosome 5 and macrophage scavenger receptor 1 (Msr1) and hemeoxigenase 1 (Hmox1) genes on chromosome 8 appear to be the major candidates.

References

• Original: J:212962 De Franco M, et al., Pristane-induced arthritis loci interact with the Slc11a1 gene to determine susceptibility in mice selected for high inflammation. PLoS One. 2014;9(2):e88302
• All: 1 reference(s)