Pgia23^DBA/1J
QTL Variant Detail

Summary

• QTL variant: Pgia23^DBA/1J
• Name: proteoglycan induced arthritis 23; DBA/1J
• MGI ID: MGI:2656616
• QTL: Pgia23 Location: Chr19:26787453-26787602 bp Genetic Position: Chr19, 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.

Pgia23, a novel locus associated with PGIA, mapped to approximately 20 cM on mouse Chromosome 19 with peak marker D19Mit30. Pgia23 is linked to IL-6 production (LOD=3.1).

A novel locus associated with CIA, Cia12, maps to 1 cM on mouse Chromosome 19 flanked by markers D19Mit59 and D19Mit93. Cia12 is linked to total arthritis score (LOD=3.1).

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.

Pgia23 mapped to proximal mouse Chromosome 19 in association with PGIA susceptibility (LOD=3.5) in the MHC-unmatched (BALB/c x DBA/1J)F2 population. Pgia23 overlaps with Cia12.

9.10.2015 - Curators Note: The distal QTL on Chr 19 linked with severity is referred to as Pgia12 within the text. However, since Pgia12 was originally mapped in J:66460 in 1999 using a (BALB/cCrl x DBA/2Crl)F2 cross, which differs from the cross used here ((BALB/c x DBA/1J)F2), we consider the current study a separate mapping study and have name the QTL Pgia42.

Pgia42 mapped to distal mouse Chromosome 19 in association with PGIA severity (LOD=4.5) in the MHC-unmatched (BALB/c x DBA/1J)F2 population.

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)