Ciaaq1^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Ciaaq1^DBA/1J
• Name: collagen induced arthritis autoantibody QTL 1; DBA/1J
• MGI ID: MGI:3716484
• QTL: Ciaaq1 Location: unknown Genetic Position: Chr7, cM position of peak correlated region/allele: 31.44 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/1J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased IgG2a autoantibody production compared to FVB/NJ. (J:122919)
• Inheritance: Dominant

Notes

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

J:122919

Advanced intercross lines (AIL) derived from DBA/1J and FVB/NJ were used to identify genetic loci associated with collagen-induced arthritis traits. A total of 308 AIL mice at the F11 or F12 generation were genotyped for 109 polymorphic markers on mouse Chromosomes 2, 5, 7, and 10. The average intermarker distance is 5.5 Mb. Animals were immunized with bovine collagen II at 8-12 weeks of age.

Linkage to collagen II-specific IgG2a autoantibody production mapped to 25 cM on mouse Chromosome 7 near D7Mit193 (LOD=4.5) and is named Ciaaq1 (collagen induced arthritis autoantibody QTL 1). The Ciaaq1 QTL interval spans 15 Mb. DBA/1J-derived alleles at Ciaaq1 confer increased IgG2a autoantibody production with a dominant mode of inheritance. Sle3 (15 cM) is a previously identified lupus QTL mapping near this region. The Ciaaq1 locus is also syntenic to a region on human Chromosome 19q13.3-19q13.4 associated with autoimmune disease susceptibility in humans.

Linkage to reactive oxygen species (ROS) production in female mice mapped to 18 cM on mouse Chromosome 7 near D7Mit228 (LOD=4.8). This locus spans an 8 Mb interval and is named Rosq1. DBA/1J-derived alleles at Rosq1 confer increased ROS production in females with an additive mode of inheritance. This alleleis also associated with increased CIA severity. Potential candidate genes for Rosq1 include Gprc2a-rs5 and Gprc2a-rs1 (20 cM).

Linkage to CD8+ T cell population in lymph nodes mapped to 69 cM on mouse Chromosome 2 near D2Mit396 (LOD=4) and 45 cM on mouseChromosome 5 near D5Mit312 (LOD=3.3). The chromosome 2 locus spans 14 Mb and is named Lctlp1 (lymph node cytotoxic lymphocyte percentage 1). The chromosome 5 locus spans 8 Mb and is named Lctlp2. DBA/2J-derived alleles at Lctlp1 and Lctlp2 confer increased CD8+ T cell populations with an additive mode of inheritance at both loci. At Lctlp1, FVB/NJ-derived alleles confer increased CD4+ T cell populations. FVB/NJ-derived alleles at Lctlp1 and Lctlp2 are also associated with increased CIA severity and earlier CIA onset. Cd8ts1 (26 cM), Pcd8ts1 (61 cM), and Eae39 (56 cM) are previously identified QTLs mapping near Lctlp2.

References

• Original: J:122919 Yu X, et al., Using an advanced intercross line to identify quantitative trait loci controlling immune response during collagen-induced arthritis. Genes Immun. 2007 Jun;8(4):296-301
• All: 1 reference(s)