Pgia11^DBA/2Crl
QTL Variant Detail

Summary

• QTL variant: Pgia11^DBA/2Crl
• Name: proteoglycan induced arthritis 11; DBA/2Crl
• MGI ID: MGI:2157157
• QTL: Pgia11 Location: Chr18:76914184-76914293 bp Genetic Position: Chr18, cM position of peak correlated region/allele: 51.91 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2Crl

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:66460

(BALB/cCrl x DBA/2Crl)F2 animals were screened for 106 polymorphic markers on 19 autosomes at an average marker spacing of 15 cM (94% coverage of genome) to identify QTLs associated with rheumatoid arthritis (RA) phenotypes (autoantibody production and inflammation). Parental inbred strain BALB/cCrl is susceptible to RA when immunized with cartilage proteoglycan whereas DBA/2Crl is resistant to RA. (BALB/cCrl x DBA/2Crl)F1 animals exhibit arthritis resistance similar to parental strain DBA/2Crl. 12 Pgia (proteoglycan induced arthritis) QTLs were identified. Pgia1 affects autoantibody production and maps to mouse Chromosome 1 at 24 cM in linkage with D1Mit170 (LOD = 4.3). Pgia2 affects autoantibody production and maps to mouse Chromosome 2 at 80 cM in linkage with D2Mit166 (LOD = 11.1). Pgia3 affects autoantibody production and inflammation and maps to mouse Chromosome 7 at 40 cM in linkage with D7Mit62 (LOD = 5.3). Pgia3 maps near Lmb3, a QTL associated with Lupus in MRL and C57BL/6 F2 mice. Pgia4 affects autoantibody production and maps to mouse Chromosome 8 at 16 cM in linkage with D8Mit224 (LOD = 18.9). Pgia5 affects inflammation and maps to mouse Chromosome 9 at 36 cM in linkage to D9Mit104 (LOD = 10.1). Pgia6 affects autoantibody production and mapsto mouse Chromosome 10 at 16 cM in linkage to D10Mit282 (LOD = 7.1). Pgia7 affects autoantibody production and maps to mouse Chromosome 11 at 34 cM in linkage to D11Mit90 (LOD = 16). Pgia8 and Pgia9 both affect inflammation and map to mouse Chromosomeosome 15 at 20 cM (LOD = 8.4 at D15Mit7) and 41 cM (LOD = 6 at D15Mit41), respectively. Pgia8 maps near Eae2, a QTL associated with experimentally induced allergic encephalomyelitis. Pgia10 affects autoantibody production and inflammation and maps to mouse Chromosome 16 at 66 cM in linkage to D16Mit152 (LOD = 8.0). Pgia11 affects autoantibody production and maps to mouse Chromosome 18 at 50 cM in linkage to D18Mit80 (LOD = 11.9). Pgia12 affects inflammation and maps to mouse Chromosome 19 at 54 cM in linkageto D19Mit71 (LOD = 8).

J:89536

Linkage analysis at an average resolution of 10 cM was performed on 3 separate mouse crosses to map QTLs associated with proteoglycan-induced arthritis (PGIA) and collagen-induced arthritis (CIA).

559 (BALB/c x DBA/2)F2 MHC-matched animals and 402 (BALB/c x DBA/1J)F2 MHC-unmatched animals were analyzed for linkage to PGIA.

537 (BALB/c x DBA/1J)F2 animals were analyzed for linkage to CIA. With respect to PGIA, parental strain BALB/c is highly susceptible whereas parental strains DBA/2 and DBA/1J are fullyresistant. As expected, (BALB/c x DBA/2)F1 hybrids are resistant to PGIA, but interestingly (BALB/c x DBA/1J)F1 hybrids are susceptible to PGIA. This is unusual because the BALB/c allele typically exhibits recessive susceptibility to disease, but thisisnot the case with the cross to DBA/1J.

With respect to CIA, parental strain DBA/1J is highly susceptible where as parental strains BALB/c and DBA/2 are fully resistant. All F1s exhibited susceptibility to CIA.

Pgia11 mapped to central mouse Chromosome 18 in association with PGIA susceptibility and severity (LOD=3.5) in the MHC-matched (BALB/c x DBA/2J)F2 population.

References

• Original: J:66460 Otto JM, et al., Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis. Arthritis Rheum. 1999 Dec;42(12):2524-31
• All: 2 reference(s)