Experiment
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) H2q/Rhd, B10.D1-(D6Mit268-D6Mit65) H2q/Rhd and B10.D1-(D14Mit212-D14Mit160) H2q/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 Cia6c, mapping to peak marker D6Mit74 on chromosome 6, was represented by a weak interaction with Cia6a that affected the severity of arthritis and an interaction with Cia49 affecting IgG1 production.
In congenic mice Cia6c, peak marker D6Mit74, increased IgG1 (p=0.003), IgG2a (p=0.007) and IgG3 (p=0.005) production in female mice but not in males. Disease susceptibility was not significantly affected in either sex. Figure 1 displays the QTL mapping between D6Mit207 and D6Mit17.
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