Pgia6^DBA/2Crl
QTL Variant Detail

Summary

• QTL variant: Pgia6^DBA/2Crl
• Name: proteoglycan induced arthritis 6; DBA/2Crl
• MGI ID: MGI:2157145
• QTL: Pgia6 Location: Chr10:20810171-20810295 bp Genetic Position: Chr10, cM position of peak correlated region/allele: 9.75 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
• Mutation: Undefined
• This allele confers resistance to autoantibody production compared to BALB/cCrl.
• Inheritance: Not Specified

Notes

Heterozygosity at Pgia6 in conjunction with DBA/2Crl-derived alleles at Pgia25 confers lower arthritis onset and incidence (susceptibility).

Pgia6 interacts with Pgia25 on chromosome X. Animals homozygosous for BALB/cCrl or DBA/2Crl alleles at Pgia6 and homozygous for DBA/2Crl alleles at Pgia25 exhibit increased arthritis onset scores.

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 Chromosome 15at 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 linkage to D19Mit71 (LOD = 8).

J:84150

Linkage analysis was performed on 559 proteoglycan-immunized (BALB/cCrl x DBA/2Crl)F2 animals to detect QTLs associated with arthritis susceptibility, severity, and onset. BALB/cCrl females are 100% susceptible to proteoglycan-induced arthritis (PGIA) whereas DBA/2Crl males are resistant. F1 hybrid males and females are also resistant to PGIA.

Several previously identified PGIA loci were confirmed in this study. These include Pgia1, Pgia4, Pgia6, Pgia7, Pgia8, Pgia9, and Pgia12.

Pgia1 mapped to mouse chromosome 1 with LOD=3.1 at D1Mit445 for arthritis severity in male mice. The Pgia1 interval spanned 33-106cM on chr 1.

Pgia4 mapped to mouse chromosome 8 with LOD=3.9 at D8Mit224 for arthritis severity for all F2 mice. The Pgia4 interval spanned 1-22cM onchr8.

Pgia6 mapped to mouse chromosome 10 with LOD=3.5 at D10Mit40 for disease onset in female mice. The Pgia6 interval spanned 30-40cMs on chr 10.

Pgia7 mapped to mouse chromosome 11 with LOD=3.1 at D11Mit132 for disease susceptibility in female mice. The Pgia7 interval spanned 42-70cM on chr 11.

Pgia8 mapped to mouse chromosome 15 with LOD=3.5 at D15Mit252 for arthritis severity in female mice. The Pgia8 interval spanned 0-20cM on chr 15.

Pgia9 mapped to mouse chromosome 15 also, with LOD=3.0 at D15Mit28 for arthritis severity in males. The Pgia9 interval spanned 30-55cM on chr15.

Pgia12 mapped to mouse chromosome 19 with LOD=4.4 at D19Mit30 for disease onset in all F2 mice. The Pgia12 interval spanned 11-33cM on chr 19.

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 this isnot the case with the cross to DBA/1J. With respect to CIA, parental strain DBA/1J is highly susceptible whereas parental strains BALB/c and DBA/2 are fully resistant. All F1s exhibited susceptibility to CIA.

Pgia6 mapped to central mouse Chromosome 10 inassociation with PGIA susceptibility (LOD=3) and onset (LOD=4.5) in the the MHC-matched (BALB/c x DBA/2)F2 population. This locus overlaps with Cia8.

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: 4 reference(s)