Cia50^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Cia50^DBA/1J
• Name: collagen induced arthritis QTL 50; DBA/1J
• MGI ID: MGI:5635551
• QTL: Cia50 Location: Chr14:54430185-54430320 bp Genetic Position: Chr14, 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, Cia50 was detected on chromosome 14 in the single locus scan at peak marker D14Mit82 where it affected total antibody production (total IgG LOD 5.3). Cia50, in interaction with Cai49, increased theincidence and the onset of disease.

In the congenic strains Cia50, at peak marker D14Mit142, increased the accumulated arthritis score and production of antibodies in a sex specific mannner. Male mice suffered increased susceptibility (p = 0.04) and higher anitbody titres (p=0.002 for IgG1, p=0.02 for IgG2a and p=0.002 for IgG3). No effect was seen in female mice. Figure 1 displays this QTL mapping between D14Mit82 and D14Mit155.

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)