Cia6a^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Cia6a^DBA/1J
• Name: collagen induced arthritis QTL 6a; DBA/1J
• MGI ID: MGI:5635520
• QTL: Cia6a Location: Chr6:29117971-29118069 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: DBA/1J

Variant description

• Allele Type: QTL

Notes

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

J:201946

Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA) in mice. In this study a known locus, Cia6, and a genomic region of Chromosome 14 were dissected using a partial advanced intercross (PAI) and a collection of congenic strains.

The congenics used for the PAI [[B10.D1-(D6Mit86-D6Mit188) H2^q/Rhd, B10.D1-(D6Mit268-D6Mit65) H2^q/Rhd and B10.D1-(D14Mit212-D14Mit160) H2^q/Rhd] were produced as speed congenics by marker assisted backcrossing of the susceptible DBA/1 (DQ) mice to the resistant, recipient strain C57BL/10.Q for seven generations. Four hundred and eighty four male, mice were tested in arthritis experiments. Seven markers were either linked to arthritis in single locus scans or involved in significant interactions detected in a two-locus scan.

To confirm and further define the indicated locus regions, subcongenic strains were produced by backcrossing selected DBA/1 fragments from the PAI to the B10.Q background. Two hundred and fifty six heterozygous, male mice and 273 heterozygous, female mice were tested for CIA susceptibility and antibody production. The peak markers and marker intervals found in the congenic mice correlated well with the loci found in the PAI. Three new loci were detected on Chromosome 6 and four new loci on Chromosome 14.

In the PAI, neighboring markers Cia6a (peak marker D6Mit307) and Cia6b (peak marker interval D6Mit268-D6Mit90) were both linked to protection from the disease. Linkage data suggests that the two markers are two distinct loci. Cia6a was linked to the onset of disease (LOD 4.6) and to total IgG production (LOD 3.3). Cia6b was linked to both onset (LOD 5.3) and incidence of disease (LOD 2.3) as well as IgG2a production (LOD 3.8). There was an epistatic interaction between the two loci affecting the onset of disease.

The congenic mice had significantly lower incidence (p=0.004), accumulated score (p=0.04), IgG1 (p=0.002), IgG2a (p=0.0002) and IgG3 (p=0.0001) in both males and females. However, the recombinations available were not sufficient to split the two loci.

References

• Original: J:201946 Popovic M, et al., Identification of new loci controlling collagen-induced arthritis in mouse using a partial advanced intercross and congenic strains. Scand J Immunol. 2008 Oct;68(4):405-13
• All: 1 reference(s)