Pgia3^DBA/2Crl
QTL Variant Detail

Summary

• QTL variant: Pgia3^DBA/2Crl
• Name: proteoglycan induced arthritis 3; DBA/2Crl
• MGI ID: MGI:2156701
• QTL: Pgia3 Location: Chr7:84290094-84290240 bp Genetic Position: Chr7, cM position of peak correlated region/allele: 48.36 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
• Mutation details: This allele confers susceptibility to autoantibody production and inflammation compared to BALB/cCrl. (J:66460)
• 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 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: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 arefullyresistant. 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.

The PGIA QTL identified here on Chr 7 was equated with Pgia3, previously mapped using the same mouse population, (BALB/cCrl x DBA/2Crl)F2, in J:66460 in 1999. Pgia3 mapped to central mouse Chromosome 7 in association with PGIA susceptibility (LOD=3) and onset (LOD=5) in the MHC-matched (BALB/c x DBA/2)F2 populations.

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, Pgia12.

The authors refer to QTL Pgia21 on Chromosome 7. Pgia21 was originally mapped using (BALB/cCrl x DBA/1J)F2 mice in J:82081 which differs from the cross used here.

We have equated the QTL identified here on Chr 7 with Pgia3, also mapped using a (BALB/cCrl x DBA/2Crl)F2 cross in J:66460 in 1999. Pgia3 maps to mouse chromosome 7 at D7Mit120 with LOD=4.8 for disease susceptibility in female mice; LOD=2.5 for disease onset in all F2 mice; and LOD=3.9 for severity in all F2 mice. The Pgia3 interval spanned 23-44cM on chr 7.

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: 1 reference(s)