Pgia20^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Pgia20^DBA/1J
• Name: proteoglycan induced arthritis 20; DBA/1J
• MGI ID: MGI:2656600
• QTL: Pgia20 Location: Chr17:74107651-74107803 bp Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: DBA/1J

Variant description

• Allele Type: QTL

Notes

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

J:82018

135 SSLP markers were screened in a set of 939 (BALB/cCrl x DBA/1J)F2 intercross animals to identify QTLs associated with collagen-induced arthritis (CIA) and proteoglycan-induced arthritis (PGIA). Parental strain BALB/cCrl is CIA-resistant and PGIA-susceptible while parental strain DBA/1J is CIA-susceptible and PGIA-resistant.

A major locus was identified on mouse Chromosome 17 in linkage to both CIA (LOD=21) and PGIA (LOD=6). This locus, Pgia17, has been previously identified and maps to proximal Chromosome 17.

A novel locus, Pgia20, maps to the same chromosome at approximately 45cM with peak marker D17Mit93. Pgia20 is linked to arthritis score (LOD=3.8) and binary arthritis susceptibility (LOD=3.4) and disease onset (LOD=4.6).

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 whereas parental strains BALB/c and DBA/2 are fully resistant. All F1s exhibited susceptibility to CIA.

Linkage to arthritis susceptibility, LOD=21.0, designated as mCia1 in Fig 3 and assigned symbol Cia1; and PGIA (LOD=6.0) were detected at the H2 locus on mouse Chromosome 17 in the (BALB/c x DBA/1J)F2 MHC-unmatched population. The PGIA locus has been mapped in previous experiments (J:78168) and is named Pgia37.

Pgia20 mapped to distal mouse Chromosome 17 in (BALB/c x DBA/1J)F2 animals (independent of MHC), and is involved in PGIA susceptibility and severity.

References

• Original: J:82018 Adarichev VA, et al., Combined autoimmune models of arthritis reveal shared and independent qualitative (binary) and quantitative trait loci. J Immunol. 2003 Mar 1;170(5):2283-92
• All: 2 reference(s)