Pgia1^DBA/2Crl
QTL Variant Detail

Summary

• QTL variant: Pgia1^DBA/2Crl
• Name: proteoglycan induced arthritis 1; DBA/2Crl
• MGI ID: MGI:2154314
• QTL: Pgia1 Location: Chr1:36065351-36065454 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: DBA/2Crl

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Susceptibility to arthritis and autoantibody production are increased in a heterozygous background. (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: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.

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)