Cia49^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Cia49^DBA/1J
• Name: collagen induced arthritis QTL 49; DBA/1J
• MGI ID: MGI:5635547
• QTL: Cia49 Location: Chr14:46996994-46997133 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, Cia49 was detected on chromosome 14 in the single locus scan at peak interval between D14Mit141 and D14Mit62 where it affected antibody production (IgG1, LOD 4.1). Cia49 interacted withCia50 to increase CIA incidence and the day of onset of the disease. It also affected IgG1 production by interacting with Cia52.

In the congenic strains Cia49, peak marker D14Mit141, significantly increased the production of antibodies in female mice (p=0.01 for IgG1,p = 0.008 for IgG2a and p=0.008 for IgG3). However there was a tendency towards lower disease scores in the Cia49 females. Figure 1 displays the QTL mapping between D14Mit140 and D14Mit4.

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)